Q4 2021 Selecta Biosciences, Inc. Earnings Call
Good morning, and welcome to the Selecta Biosciences fourth quarter and full year 2021 Financial Results and Corporate Update conference call. Currently, all participants
Good morning, and welcome to the select that Biosciences fourth quarter and full year 2021 financial results and corporate update conference call.
Currently all participants are in a listen only mode.
This call is being webcast live on the Investors & Media section of Selective's website at www.selectabio.com and it is being recorded.
This call is being webcast live on the investors and media section of select its website at www dot select the buyer dot com and it is being recorded.
For opening remarks, I would like to introduce Kevin Tan, Chief Financial Officer of Selecta. Please go ahead. Thank you, Kevin.
For opening remarks, I would like to introduce Kevin Tan Chief Financial Officer of Selecta. Please go ahead.
Kevin Tan: Thank you and good morning. Welcome to our fourth quarter and full year 2021 financial results and corporate update conference call.
Thank you and good morning, welcome to our fourth quarter and full year 2021 financial results and corporate update conference call.
Kevin Tan: The press release reporting our financial results is available in the Investors and Media section of Selective's website, www.selectivebio.com, and our annual report on Form 10-K for the year ended December 31, 2021, which will be filed today with the Securities and Exchange Commission, or SEC.
The press release reporting our financial results is available in the investors and media section select US website worldwide web selected bio dot com and our annual report on Form 10-K for the year.
Ended December 31, 2021, which will be filed today with the securities and Exchange Commission or SEC.
Kevin Tan: Joining me today are Carson Brun, President and Chief Executive Officer, and Peter Traver, Chief Medical Officer.
Joining me today are Carson, Brewin, President and Chief Executive Officer, and Peter Traber, Chief Medical Officer.
Kevin Tan: During today's call, we will be making certain forward-looking statements, including without limitation statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, financial projections, and our future expectations, plans, partnerships, and prospects.
During today's call, we will be making certain forward looking statements, including without limitation statements about the potential safety.
We can see and regulatory and clinical progress of our product candidates financial projections and our future expectations.
<unk> partnerships and prospects.
Kevin Tan: These statements are subject to various risks that are described in the filings made with the SEC, including the most recent annual report on Form 10-K .
These statements are subject to various risks that are described in our filings made with the SEC, including the most recent annual report on Form 10-K .
Kevin Tan: Your college will not place undue reliance on these forward-looking statements, which speak specifically to March 10, 2022, and selectively disclaims any obligation to update such statements, even if management's views change.
You are cautioned not place undue reliance on these forward looking statements which speak.
March 10 2020 to.
<unk> disclaims any obligation to update such statements.
If management's views change.
I would now like to turn the call over to Carsten Brunn Carson.
Speaker Change: Thank you, Kevin. Good morning. I appreciate everyone joining us today.
Thank you Kevin Good morning, I appreciate everyone joining us today.
Speaker Change: Before we begin, I'm thrilled to announce that on March 9th the FDA cleared the Investigational New Drug or IMD application for a Phase I gene therapy clinical trial of STL302 to treat methicolonic acidemia or MMA, a serious and life-threatening metabolic disorder.
Before we begin I'm thrilled to announce that on March nine the FDA cleared the investigational new drug or IND application for a phase one gene therapy clinical trial as the L. Three O two to treat medical malonic academia or MMA.
Serious and life threatening metabolic disorder.
Speaker Change: This clinical trial is a critical step in our efforts to treat MMA and enable redosing of AEV-mediated gene therapies. We expect to initiate the Phase I trial in the second half of 2022, and we look forward to bringing hope to all those patients and families affected by this terrible disease.
This clinical trial is a critical step in our efforts to treat MMA and enable re dosing of AAV mediated gene therapies.
To initiate the phase one trial in the second half of 2022, and we look forward to bringing hope to all those patients and families affected by this terrible disease.
Speaker Change: 2021 was a very busy and transformational year, and we're extremely pleased with the significant progress to propel our business forward.
2021 was a very busy and transformational year and we're extremely pleased with the significant progress to propel our business forward.
Speaker Change: Over the past year, we advanced our pipeline of wholly owned and partnered programs. We entered a number of key strategic partnerships and are close to catalyzing an evolution of our precision immune tolerance platform.
For the past year, we advanced our pipeline of wholly owned and partnered programs. We entered a number of key strategic partnerships and are close to Catalyzing, an evolution of our position immune tolerance platform <unk>.
Speaker Change: By combining mTOR with a TREC-selective IL-2 molecule, we've observed synergistic effects in the induction and expansion of antisynthesitic regular T-cells for TREC.
Binding in tour with a T Rex selective IL two molecule.
Sure.
<unk> effects in the induction and expansion of Amazon Pacific regulatory T cells or T. Rex we.
Speaker Change: We believe this transformative combination, which we call IMTOR-IL, has the potential to enhance the induction and durability of antigen-specific immune tolerance, a substantial leap forward for our IMTOR platform.
We believe this transformative combination, which we call into or IL has the potential to enhance the induction and durability of antigen specific immune tolerance, a substantial leap forward for into our platform.
Speaker Change: I would now like to walk you through key updates and recent strategic partnerships pertaining to the three pillars of our pipeline. Reimagining immunotherapy.
I would now like to walk you through key updates and recent strategic partnerships pertaining to the three pillars of our pipeline.
Re imagining immunotherapy for autoimmune disease.
Speaker Change: Unlocking the potential of adeno-associated virus or AAV gene therapy, and amplifying the efficacy of biologics.
Unlocking the potential of Athena associated virus or AAV gene therapy.
And amplifying the efficacy of biologics.
Speaker Change: The current standard of care for autoimmune diseases is broad immune suppression, which is associated with side effects that often leave patients vulnerable to serious infection and malignancy.
The current standard of care for autoimmune diseases is broad immune suppression, which is associated with side effects that often leave patients vulnerable to serious infections and malignancies.
Speaker Change: By reimagining immunotherapy for autoimmune diseases, we have taken important steps to address the significant need for antigen-specific therapies without chronic and systemic immune suppression.
By re imagining immuno therapy for autoimmune diseases, we have taken important steps to address the significant need for an specific therapies without chronic and systemic immune suppression.
Speaker Change: I want to start out with our most exciting finding from the last 12 months.
I wanted to start out with our most exciting finding from the last 12 months.
Speaker Change: In recent preclinical data generated by our scientific teams, we observed that mTOR showed profound synergistic activity when combined with engineered IL-2 molecules that are selected for TREC.
In recent preclinical data generated by our scientific teams, we observed that in towards showed profound synergistic activity when combined with engineered IL two molecules that are selective for T. Rex.
Speaker Change: Mice harboring transgenic antigen-specific T-cells were dosed with the target antigen and then treated with Imtor IL, a combination of Imtor and a T-Rex selective IL-2.
Mice, harboring transgenic and specific T cells for dose with a target antigen and then treated with <unk> L. A combination of <unk> and a T T Rex selective IL two.
Speaker Change: We observed mTOR alone to induce Anderson-specific T-rex, and from my extensive clinical experience with mTOR, find this level of T-rex induction to be clinically meaningful.
We observed inventory loan to induce and specific T Rex and for my extensive clinical.
Experience with Infor find its level of tumor conduction to be clinically meaningful.
Speaker Change: Interestingly, the administration of IMTOR-IL combined with the target antigen led to a substantially greater increase in antigen-specific Tregs.
Interesting interestingly the administration of <unk> combined with the target Amazon led to a substantially greater increase in Edison and Pacific Cubic's. In contrast, mice dose with the engineered IL two plus antigen should only an expansion of total T Rex, but little or no.
Speaker Change: In contrast, mice dosed with the engineered IL-2 plus antigen took only an expansion of total T-Rex, but little or no expansion of any specific T-Rex.
Expansion of any specific T Rex.
Speaker Change: We believe mTOR-IL is a transformative evolution of our precision immune tolerance platform with implications across our entire pipeline.
We believe <unk> is a transformative evolution of our precision immune tolerance platform with implications across our entire pipeline.
Speaker Change: Importantly, InterRL has the potential to unlock treatments for patients with a variety of autoimmunity disorders.
Importantly, <unk> has the potential to unlock treatments for patients with a variety of autoimmune diseases.
Speaker Change: We also tested IMTOR-L in an animal model for the ability to induce durable immune tolerance to a co-administered AAV gene therapy.
We also tested into I L. In an animal model for the ability to induce durable immune tolerance to a court minister AAV gene therapy.
Speaker Change: In this study, MTOR-IL was co-administered with two doses of an AAV vaccine.
In this study into IL was co administered with two doses of an AAV vector.
Speaker Change: we observed complete inhibition of anti-AEB antibody formation after multiple vector doses through 117 days. And most excitingly, this synergistic effect was observed at doses that are considered sub-therapeutic for intralong.
We observed complete inhibition anti AAV antibodies formation after multiple vector doses through 117 days and most Excitingly is this synergistic effect was observed at doses that are considered sub therapeutic for into a loan.
Speaker Change: These results suggest that the addition of a T-rex selective IL-2 to mTOR has the potential to increase the potency, durability, and potentially allow for dose sparing of mTOR.
These results suggest that the addition of a T. Rex selective IL two two <unk> has the potential to increase the potency durability and potentially allow for dose sparing off in tour.
Speaker Change: Current programs of engineered IL-2 molecules in development for autoimmune diseases focus on non-selective expansion of total existing T-rex, but not T-rex specific for the autoantigens that drive the pathogenesis of the disease.
Current programs of engineered IL two molecules in development for autoimmune diseases focused on non selective expansion of total existing T Rex, but not T. Regs specific for the <unk> engine that drives the pathogenesis of the disease.
Speaker Change: mTOR-IL has the potential to be a truly differentiated first-in-class, Anderson-specific immunotherapy that restores balance in vivo to the millions of patients suffering from autoimmune disease today.
<unk> has the potential to be a truly differentiated first in class Anderson specific immunotherapy that restores balanced in vivo to the millions of patients suffering from autoimmune disease today.
Speaker Change: On September 8, 2021, we entered into a collaboration with Cyrus Biotechnology, a world-leading protein engineering company to design a next-generation proprietary T-Rex selective IL-2 molecule.
On September eight 2021, we entered into a collaboration with Cyrus Biotechnology, a world leading protein engineering company to design and next generation proprietary T. Rex selective IL two molecule.
Speaker Change: A key priority for 2022 will be to identify target indications and accelerate the development of mTOR IL into the clinic.
A key priority for 2022 will be to identify target indications and accelerated development of <unk> into the clinic in parallel we are continuing our IND, enabling studies for our primary biliary cholangitis or PBC program.
Speaker Change: In parallel, we are continuing IND-enabling studies for our primary bilirongitis, or PBC, program.
Moving onto our work in gene therapy in.
Speaker Change: In 2021, we reported with our partner Aspire on a clinical proof-of-concept study of mTOR combined with an AEV empty capsid in healthy volunteers, which I'll expand on later.
In 2021, we reported with our partner asked by them on the clinical proof of concept study of <unk> combined with an AAV empty capsid in healthy volunteers, which I'll expand on later.
Speaker Change: We also published preclinical studies in Science Advances describing the first dose benefit of mTOR on enhancing transient expression when co-administered with the initial dose of an AAV vector.
We also published preclinical studies in science advances, describing the first dose benefits off in tour on enhancing transient expression when co administered with the initial dose pump an AAV vector.
Speaker Change: In addition, we published a paper in Frontiers Immunology describing the potential hepatoprotective properties of mTOR.
In addition, we published a paper in frontier immunology, describing the potential hit by the protective properties off into her.
Speaker Change: These findings build on the growing body of evidence demonstrating the potentially multi-faceted benefits of mTOR for enhancing the efficacy and safety of AAV genes therapy.
These findings build on the growing body of evidence demonstrating the potentially multifaceted benefits off into or for enhancing the efficacy and safety of AAV gene therapy.
Speaker Change: On October 4th, 2021, we entered a strategic license agreement with Takeda, a global pharmaceutical leader with expertise in rare diseases, to combine mTOR with their targeted next-generation gene therapies for two lysosomal storage disorders.
On October four 2021, we entered a strategic license agreement with Takeda, a global pharmaceutical leader with expertise in rare diseases.
Buying in tour with their targeted next generation gene therapies for two licenses almost storage disorders.
Speaker Change: We're encouraged by the strong endorsement from one of the leaders in the lysosomal storage disorder landscape as a validation of our approach and precision immune tolerance platform.
Courage by the strong endorsement from one of the leaders in the licensed <unk> storage disorder landscape as a validation of our approach and precision immune tolerance platform.
Speaker Change: We look forward to working closely with and supporting Takeda.
Look forward to working closely with and supporting Takeda.
Speaker Change: We also continue to seek partnerships to expand our platform with technologies that can be applied to mitigating immunogenicity of AAV gene therapy.
We also continue to seek partnerships to expand our platform with technologies that can be applied to mitigating immunogenicity of AAV gene therapies.
Speaker Change: On October 21st, 2021, we announced an exclusive license agreement with Genovis to advance ZURK, a differentiated IgG protease, to enable the dosing of transformative gene therapies in patients with pre-existing anti-AAV immunity.
On October 21, 2020 , one we announced an exclusive license agreement with <unk> to advance absorbed a differentiated ITG protease to enable the dosing of transformative gene therapies in patients with preexisting anti AAV immunity.
Speaker Change: Currently, up to 50% of the potential patient population for gene therapy trials are ineligible for inclusion due to preexisting neutralizing anti-AEB antibodies that are a result of natural infection with wild-type AEB.
Currently up to 50% off the potential patient population for gene therapy trials are in eligible for inclusion due to preexisting neutralizing anti AAV antibodies that are result of naphthalene infection with the wild type AAV that many patients in need.
Speaker Change: Thus, many patients in need are unable to access potentially life-altering treatments for their genetic diseases, for which there may be few or no treatment alternatives.
Unable to access potentially life altering treatments for their genetic diseases for which there may be few or no treatment alternatives.
Speaker Change: Zork is a bacterial protease that is designed to specifically cleave human IgG and is being developed as a pre-treatment in advance of an AAV gene therapy with the goal of transitively clearing pre-existing neutralizing antibodies to create a treatment window during which gene therapy can be administered.
<unk> is a bacterial protease that is designed to specifically cleave human ITG and is being developed as a pre treatment in advance of an AAV gene therapy with the goal of transit the clearing preexisting neutralizing antibodies to create a treatment window.
Which gene therapy can be administered.
Speaker Change: ZORC is differentiated from some other IgG-proteases in that ZORC is derived from a non-human pathogen and therefore has demonstrated very low cross-reactivity to pre-existing anti-IgG-protease antibodies.
<unk> is differentiated from some other ITG proteases in that <unk> is derived from a non human pathogen and therefore has demonstrated very low cross reactivity to preexisting anti ITG fortyish antibodies.
Speaker Change: The combination of Zork and Imtor has the potential to address two of the biggest issues currently limiting AAV gene therapy.
The combination of <unk> and <unk> has the potential to address two of the biggest issues currently limiting AAV gene therapy zorba to bring the power of gene therapies to those patients who would be otherwise and eligible for treatment to their preexisting antibodies and in tour to mitigate the normally been risk.
Speaker Change: Zort to bring the power of gene therapies to those patients who would be otherwise ineligible for treatment due to pre-existing antibodies, and Intor to mitigate the normal immune responses to AAV gene therapy and in AAV.
Sponsors to AAV gene therapy.
And enable re dosing.
Speaker Change: We believe that the combination of Zorc and Imtor has the potential to provide safer and more effective gene therapies to more patients.
We believe that the combination absorbed and <unk> has the potential to provide safer and more effective gene therapies to more patients.
Speaker Change: We also announced a collaboration with Ginkgo Bioworks on January 10, 2022, to design novel AAV capsids with a goal of improving transduction efficiency, liver tropism, and immunogenicity profile.
We also announced a collaboration with Ginkgo Bio works on January 10, 2022 to design novel AAV capsid with a goal of improving transduction efficiency Libert tropism and Immunogenicity profile in.
Speaker Change: Dinko will design and engineer the capsids, and Selecta will conduct all nonclinical and clinical studies thereafter.
Ginkgo will design and engineered the cap suits and selected will conduct all non clinical and clinical studies thereafter.
Speaker Change: This partnership leverages ginkgo cell engineering and high throughput screening capabilities and select us into our precision immune tolerance platform to advance gene therapy delivery.
This partnership Leverages, Ginkgo cell engineering, and high throughput screening capabilities and select us in tour precision immune tolerance platform to advance gene therapy delivery.
Speaker Change: A major hurdle for the gene therapy field has been the toxicity associated with high AAV dose.
A major hurdle for the gene therapy field has been the toxicity associated with high AAV doses.
Speaker Change: In many cases, the toxicity is inextricably linked to immunogenicity. Our vision is to change the treatment paradigm to dose low and slow by combining mTOR with more efficient capsids to enable administration of multiple smaller doses rather than a single high AAV dose, which is often associated with serious adverse events.
In many cases, the toxicity is inextricably linked to Immunogenicity. Our vision is to change the treatment paradigm to dose low and slow by combining in tour with more efficient capsid to enable administration of multiple slow smaller doses, while they're in the single high AAV dose.
Which is often associated with serious adverse events.
Speaker Change: As mentioned earlier, in 2021, we announced top-line results from the first in-tumen phase 1 dose escalation trial of SAL-399, which we conducted jointly with our partner, Aspire.
As mentioned earlier in 2008, and 2021, we announced topline results from the first in human Phase one dose escalation trial of <unk> 399, which we conducted jointly with our partner and ask style.
Speaker Change: SAL-399 is an AV8 anti-vector capsid containing no DNA combined with mTOR at doses of 0.15 mix per kick and 0.3 mix per kick. The randomized placebo-controlled double-blind dose escalation study conducted in healthy volunteers was designed to determine the dose regimen of mTOR to mitigate the formation of neutralizing antibodies, or NAPs, against AV8 serotype capsid used in chemotherapy.
S. L 399 is an AAV eight anti vector capsid containing no DNA combined with <unk> at doses of one five mix per gig and 0.3 mix per gig.
The randomized placebo controlled double blind dose escalation study conducted in healthy volunteers was designed to determine the dose regimen of <unk> to mitigate the formation of neutralizing antibodies or naps against 88 serotype capsid used in gene therapies.
Speaker Change: We observed a strong immune response in humans administered AAV and decafsits alone.
We observed a strong immune response in humans administered AAV empty capsid alone the.
Speaker Change: The addition of mTOR to the administration of anti-CAPSIDS reduced the formation of anti-AV8 NAPs in a dose-dependent manner at day 30.
The addition of <unk> to the administration of empty capsid reduce the formation of anti AAV eight naps in a dose dependent manner at day 30.
Speaker Change: Consistent with preclinical data, we observed that the single dose of mTOR cohorts saw delayed formation of NAPs, eventually reaching similar median levels of NAPs to the control group by day 90. Based on prior animal studies, we believe that if NAPs are inhibited at day 30, administration of two additional monthly doses of mTOR has the potential to inhibit the formation of NAPs with improved durability.
Consistent with preclinical data, we observed that the single dose of intra cohorts, Saudi late formation off Naps eventually reaching similar median levels of maps to the control group by day 90.
Based on prior animal studies, we believe that he snaps are inhibited at day 30 administration of two additional monthly doses of <unk> has the potential to inhibit the formation of maps with improved durability. We.
Speaker Change: We expect that the learnings from the MCAPSIS clinical trials and our non-clinical studies, employing three monthly doses of mTOR, will guide the clinical development of our proprietary gene therapy program, STL302.
We expect that the learnings from the empty capsid clinical trials and our non clinical studies employing three monthly doses of <unk> will guide the clinical development of our proprietary gene therapy program <unk> three O two.
Speaker Change: STL3O2 is a combination of mTOR with MMA 101 and AV gene therapy being delivered for the treatment of MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats.
<unk> two is a combination off in tour with MMA eight one to one and a beach in therapy being delivered for the treatment of MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats.
Speaker Change: As previously mentioned, on March 9th, the FDA cleared the IND application for RFase 1 clinical trial of STL302 to treat MMA.
As previously mentioned on March nine the FDA cleared the IND application for a phase one clinical trial of <unk> to treat MMA.
Speaker Change: I want to thank our dedicated clinical, regulatory, and CMC teams here at Selecta and our external partners for all their hard work in addressing the clinical.
I want to thank our dedicated clinical regulatory and CMC teams here at Selecta, and our external partners for all their hard work in addressing the clinical hold.
Speaker Change: The trial is expected to initiate in the second half of 2022 and will evaluate the safety and efficacy of SCL302 and the prevention of formation of utilizing antibodies against the MMA101AV capsid.
The trial is expected to initiate in the second half of 2022 and will evaluate the safety and efficacy of <unk> hundred two and the prevention automation also utilizing antibodies against the MMA 101 AAV capsid.
Speaker Change: Our second wholly-owned proprietary gene therapy product candidate is SCL313 for the treatment of ornithine transcarbamylase deficiency.
Our second wholly owned proprietary gene therapy product candidate is <unk> 313 for the treatment of only thing turns cobham wireless deficiency.
Speaker Change: While we had originally anticipated a clinical trial application and IMD filing in 2022, we have decided to prioritize our resources on the MMA program for the time being.
We had originally anticipated clinical trial application and I N E filing in 2022, we have decided to prioritize our resources on the MMA program for the time being.
Speaker Change: Overall, we're seeing excellent progress across our gene therapy programs and look forward to continuing to progress into both our wholly owned gene therapies as well as in partnership with our leading gene therapy partners.
Overall, we are seeing excellent progress across our gene therapy programs and look forward to continuing to progress into or both our wholly owned gene therapies as well as in partnership with our leading gene therapy partners. We believe that the platform technologies into ensor position selective as a leader in unlocking.
Speaker Change: We believe that the platform technologies of Intour and Zort position Selekta as a leader in unlocking the true potential of AAV gene therapy.
The true potential of AAV gene therapy.
Speaker Change: Lastly, a few key updates on our biologics programs for our most mature pipeline tiller.
Lastly, a few key updates whenever biologics programs from our most mature pipeline pillar.
Speaker Change: Many biologics can be highly immunogenic resulting in suboptimal responses due to the development of anti-drug antibodies after multiple treatments.
Many biologics can be highly immunogenic, resulting in sub optimal responses due to the development of anti drug antibodies after multiple treatments.
Speaker Change: Patients that develop an immune response may be forced to discontinue treatment or experience adverse reactions.
Patients develop an immune response may be forced to discontinue treatment or experienced adverse reactions. We believe the use of <unk> as an adjunct to biologics offers a promising approach to minimize the health care and economic burden of antidrug antibodies.
Speaker Change: We believe the use of mTOR as an adjunct to biologics offers a promising approach to minimize the healthcare and economic burden of anti-drug antibodies.
Speaker Change: SCL 212 is comprised of IMTOR, court minister with a proprietary UL case, the Getter case, for the treatment of chronic refractory gout, and was licensed to SOBE in 2020.
<unk> is comprised of <unk> co administered with our proprietary uk's. The gastric case for the treatment of chronic refractory gout and was licensed to <unk> in 2020.
Speaker Change: As a reminder, our Phase III Dissolved Clinical Program kicked off in the third quarter of 2020 and consists of two double-blind placebo-controlled trials of SEL212.
As a reminder, our phase III resolve clinical program kicked off in the third quarter of 2020 and consists of two double blind placebo controlled trials of <unk> in.
Speaker Change: In both trials, SCL212 will be evaluated at two doses of mTOR, 0.15 mix per kick and 0.15 mix per kick, and one dose of together case, 0.2 mix per kick. Each trial aims to enroll up to 120 patients with up to 40 subjects in each of the two treatment arms and up to 40 on placebo.
In both trials SCL 212, there'll be evaluated at two doses of <unk>, one five mix per gig and one five mix per gig and one dose after Gatwick cased point to mixed.
Each trial aims to enroll up to 100 patients 120 patients with up to 40 subjects in each of the two treatment arms and up to 40 on placebo.
Speaker Change: On December 1st, 2021, we announced full enrollment of the ZOP1, which is being conducted in the United States.
On December one 2021, we announced full enrollment of dissolved one which is being conducted in the United States.
Speaker Change: Enrollment into the Dissolve II trial is ongoing and the study is being conducted in the United States and four countries across Eastern Europe .
Enrollment into the dissolved two trial is ongoing and the study is being conducted in the United States and four countries across eastern Europe .
Speaker Change: We are closely monitoring the evolving geopolitical situation in Ukraine and Russia and have proactively undertaken mitigation steps to prioritize the safety of our patients and investigators first and foremost, as well as address any potential disruption.
We are closely monitoring the evolving geopolitical situation in Ukraine, and Russia and have proactively undertaken mitigation steps to prioritize the safety of our patients and investigators first and foremost as well as address any potential disruptions, while we have some temporarily closed screening and randomization.
Speaker Change: While we have some temporarily closed screening and randomization at sites in both Russia and Ukraine due to shipping constraints, we have proactively added 11 additional sites in the United States to offset and speed enrollment in Resolve 2.
At sites in both Russia, and Ukraine due to shipping constraints, we have proactively added 11 additional sites in the United States to offset and speed enrollment and resolved too.
Speaker Change: Of these additional enrollment sites, nine have already been activated and two are pending initiation and activation.
Of these additional enrollment sites nine have already been activated and two are pending initiation and activation.
Speaker Change: We will continue to work closely with our licensing partner, SOBE, our clinical trial providers and regulatory authorities to assess the potential impact on the program.
We will continue to work closely with our licensing partners sobey, our clinical trial providers and regulatory authorities to assess the potential impact on the program.
Speaker Change: Before turning back to our pipeline and program updates, we want to emphasize that our hearts are with the people of Ukraine during this unprecedented humanitarian crisis.
Before turning back to our pipeline and program updates you want to emphasize that our hearts are with the people of Ukraine. During this unprecedented humanitarian crisis.
Speaker Change: With extensive clinical data and an asset currently in phase 3, we believe our biologics pipeline is well positioned to leverage these learnings into our second biologics indication in IgA nephropathy, a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1, or IgA1, accumulate in the kidney.
With extensive clinical data and then asset currently in phase III.
We believe our biologics pipeline is well positioned to leverage these learnings into our second largest indication in Iga nephropathy, and kidney disease kidney disease that occurs when immune complexes antibody called immuno globally in a one or Iga one accumulate in the kidneys.
Speaker Change: Current treatments fail to address the underlying pathophysiology of the disease, which are the IJ immune deposits.
Current treatments fail to address the underlying pathophysiology of the disease, which are the iga immune deposits.
Speaker Change: We believe our novel approach, which combines Intor with an IgA1 protease, has the potential to remove injurious IgA from the kidneys and improve markers of renal dysfunction.
We believe our novel approach, which combines <unk> with an Iga one protease has the potential to remove endures iga from the acuteness and improve markers of renal dysfunction.
Speaker Change: We're currently working with Igaine Biosciences on a first-generation IgA protease derived from the Haemophilus influenzae bacteria.
We're currently working with IGN Biosciences on a first generation Iga protease derived from the muscle most influenza bacteria.
Speaker Change: On October 26, 2021, we entered a collaboration with Ginkgo Bioworks to discover next-generation enzyme therapy.
On October 26, 2021, we entered the collaboration with Ginkgo bio works to discover and next generation enzymes therapies. Today, we're announcing that the first program will focus on generating a second generation protease with lower immunogenicity and potentially transformative theyre pretty potential when combined with them towards.
Speaker Change: Today, we're announcing that the first program will focus on generating a second-generation IgA protease with lower immunogenicity and potentially transformative therapeutic potential when combined with M12.
Speaker Change: We're extremely excited about these advancements and the value-driving milestones.
We're extremely excited about these advancements and the value driving milestones ahead with that I'll turn the call over to Kevin to run through our financial results for the fourth quarter and fiscal year ended December 31 2021, Kevin.
Speaker Change: With that, I'll turn the call over to Kevin to run through our financial results for the fourth quarter and fiscal year ended December 31st, 2021. Kevin. Thank you.
Thank you Carsten.
We remain well capitalized with $129 4 million in liquidity as of December 31, 2021, which compares to $140 1 million in liquidity as of December 31, 2020.
Kevin Tan: $129.4 million in liquidity as of December 31, 2021, which compares to $140.1 million in liquidity as of December 31, 2020.
Kevin Tan: We believe our liquidity will be sufficient to meet our operating requirements into the third quarter of 2027.
We believe our liquidity will be sufficient to meet our operating requirements into the third quarter of 2023.
Kevin Tan: It is important to note that this is the most conservative forecast of our cash runway.
It is important to note that this is the most conservative forecast of our cash runway.
Kevin Tan: considers none of the potential incoming milestones and royalties from our numerous partnerships.
None of the potential incoming milestones and royalties from our numerous partnerships.
Net cash used in them.
Kevin Tan: $60.4 million for the 12 months and fiscal year ended December 31st, 2021.
$50 4 million for the 12 months and fiscal year ended December 31 2021.
Kevin Tan: as compared with $34.9 million net cash provided by operating activities for the same period in 2020.
As compared with $34 9 million net cash provided by operating activities for the same period in 2020.
Kevin Tan: Collaboration and license revenue recognized for the fourth quarter and fiscal year 2021 with 29.9 million and 85.1 million.
Collaboration and license revenue recognized for the fourth quarter and fiscal year, 2021, with $29 9 million and $85 1 million compared to 12 million and $16 6 million for the same periods in 2020.
Kevin Tan: compared to $12 million and $16.6 million for the same period in 2020.
Kevin Tan: Revenue was primarily driven by the license agreement with SOBE, resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase III Dissolved Clinical Program.
Revenue was primarily driven by the license agreement with sobey, resulting from the shipment of clinical supply and the reimbursement of costs incurred for the phase III <unk> clinical program.
Kevin Tan: Additionally, during the fourth quarter, Selective recognized $1 million for shipments of clinical supply under the license agreement with Takeda and $0.4 million for shipments under the license agreement with SREPTA.
Additionally, during the fourth quarter collected recognized $1 million for shipments of clinical supply under the license agreement with Takeda and <unk> 4 million for shipments under the license agreement with <unk>.
Research and development expenses for the fourth quarter and fiscal year, 2021 were $20 3 million and $68 7 million respectively.
Kevin Tan: for the fourth quarter and fiscal year 2021 were 20.3 million and 68.7 million respectively.
Kevin Tan: which compares with $15.1 million and $54.5 million for the same periods in 2020.
Which compares with $15 1 million and $54 5 million for the same periods in 2020.
Kevin Tan: The quarterly and annual increases were primarily driven by expenses incurred for preclinical programs, payroll costs, and ask-bio collaboration costs.
The quarterly and annual increases were primarily driven by expenses incurred for preclinical programs payroll cost and <unk> bio collaboration costs.
Kevin Tan: General and administrative expenses for the fourth quarter and fiscal year 2021 were $5.5 million and $20.9 million respectively.
General and administrative expenses for the fourth quarter and fiscal year, 2021 were $5 5 million and $29 million respectively.
Kevin Tan: which compares with $4.8 million and $18.9 million for the same periods in 2020.
Which compares with $4 8 million and $18 9 million for the same periods in 2020.
Kevin Tan: The quarterly and annual increases were primarily driven by increases in stock compensation expenses and consulting fees, offset by a reduction in professional...
The quarterly and annual increases were primarily driven by increases in stock compensation expenses and consulting fees offset by a reduction in professional fees.
Kevin Tan: For the full year 2021, select to recognize an income tax expense of $6,000.
For the full year 2021 select a recognized an income tax expense of $16 million.
Kevin Tan: the expense with the result of our decision to opt out of the installment sales method that would have been applied to the sale of the SOE license for income tax purposes. By electing out of the installment method.
The expense with the result of our decision to opt out of the installment sales method that would have been applied to the sale of the <unk> license for income tax purposes.
By electing out of the installment method.
The company was taxed on an estimated fair value of the current and future proceeds from the <unk> license as part of our 2020 income tax return filings.
Kevin Tan: current and future proceeds from the SOBE license as part of our 2020 income tax return filing.
Kevin Tan: As a reminder, the SOBI Agreement provides for up to $630 million in development, regulatory, and sales milestones, as well as royalty payments based on tractual sales tiers.
As a reminder, this Kobe agreement provides for up to $630 million in development regulatory and sales milestones as well as royalty payments based on contractual sales tiers.
As a result of the collection.
Kevin Tan: any revenues resulting from these future milestones and royalties will be excluded from selective taxable income.
Any revenues, resulting from these future milestones and royalties will be excluded from select us taxable income.
Kevin Tan: For the fourth quarter and fiscal year 2021, we reported net income of $12.2 million, or basic net income per share of $0.10 per share, and net loss of $25.7 million, or basic net loss per share
For the fourth quarter and fiscal year 2021, we reported net income of $12 2 million or basic net income per share of <unk> 10 per share.
Net loss of $25 7 million or basic net loss per share of 22.
Kevin Tan: For the fourth quarter and full year 2020, we reported net losses of $15.4 million or a net loss of $0.14 per share.
For the fourth quarter and full year 2020, we reported net losses of $15 4 million or net loss of <unk> 14 per share.
Kevin Tan: 68.9 million or a net loss of 68 cents per share.
$68 9 million or a net loss of 68 per share.
Kevin Tan: I will now turn it back to Carson for closing remarks. Carson.
I will now turn it back to Carsten for closing remarks Carsten.
Carsten Brunn: Thank you, Kevin. In summary, 2021 was an incredibly productive year for Celesta. We're excited to enter the clinic with SEL 302 about the continued growth of our pipeline, our multiple shots on goal, and numerous validating partnerships.
Thank you Kevin.
In summary, 2021 was an incredibly productive year for select them. We're excited to enter the clinic with C. L. Three or two about the continued growth of our pipeline.
Multiple shots on goal and numerous validating partnerships. Furthermore, we remain confident in the broad applicability of our position immune tolerance platform to potentially restore south tolerance in autoimmune disease and overcome immunogenicity in gene therapy and biologics.
Carsten Brunn: Furthermore, we remain confident in the broad applicability of our precision immune-tolerance platform to potentially restore self-tolerance in autoimmune disease and overcome immunogenicity in gene therapies and biologics.
Carsten Brunn: We believe Intel IL, an evolution of the Intel platform, potentially represents a generational leap forward.
We believe <unk> IL and evolution of the Intel platform potentially represents a generational leap forward.
Carsten Brunn: The strong synergistic effects we've seen in our preclinical work demonstrates mTOR-L has the potential to unlock antigen-specific immunotherapies for autoimmune diseases, as well as improve the efficacy and safety profile of therapies across our.
Our strong synergistic effects, we have seen in our preclinical work demonstrates into our L has the potential to unlock and specific immunotherapies for autoimmune diseases as well as improve the efficacy and safety profile.
A therapies across our entire pipeline.
Carsten Brunn: With multiple anticipated catalysts in 2022, we look forward to providing additional updates on our progress as we explore gene therapy and aping opportunities, advance SAL302, complete the dissolved phase 3 trial of SAL212 in chronic disfector gout, and continue to expand our diversified pipeline to autoimmune diseases.
With multiple anticipated catalysts in 2022, we look forward to providing additional updates on our progress as we explore gene therapy and <unk> opportunities advance C. L. Three years to complete the dissolved phase III trial of <unk> in chronic refractory gout and continue to expand our <unk>.
<unk> pipeline two autoimmune diseases.
Carsten Brunn: Looking ahead, we believe we are well positioned to deliver on our sharpened clinical development strategy with a focus on autoimmune disease indications, explore gene therapy and aping applications, and realize the full potential of our evolving intro class.
Looking ahead, we believe we are well positioned to deliver when our sharpened clinical development strategy with a focus on autoimmune disease indications explore gene therapy, and <unk> applications and realize the full potential of our evolving into a platform.
Speaker Change: Before we conclude today's call, I would also like to thank the entire selector team.
Before we conclude today's call I would also like to thank the entire selected team.
Speaker Change: our investors, and the many people who have been supported along the way, including our patients and their families. With that, we are
Our investors and the many people who have been supported among the way, including our patients and their families.
With that we're happy to take questions.
Speaker Change: We will now begin the question and answer session. To ask a question, you may press star than one on your touchtone phone.
We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone.
Speaker Change: If you are using a speakerphone, please pick up your handset before pressing the key.
If you are using a speakerphone please pick up your handset before pressing the keys.
Speaker Change: If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster.
If at any time your question Thats been addressed and you would like to withdraw your question. Please press Star then two.
At this time, we will pause momentarily to assemble our roster.
Yes.
Okay.
Speaker Change: Our first question will come from Kristen Kluska with Cantor Fitzgerald. Please go ahead.
Our first question will come from Kristen <unk> with Cantor Fitzgerald. Please go ahead.
Kristen Kluska: Hi, good morning. Thanks for taking my questions and congrats on addressing this hold and getting it lifted in under four months.
Hi, good morning, Thanks for taking my questions and congrats on addressing this hold in getting it lifted it under four months. So wanted to ask at a high level you could talk about some of the CMT related items for this hold and by addressing these now do you think that running future studies weathering MMA or other.
Kristen Kluska: So, I wanted to ask at a high level if you could talk about some of the CMC-related items for this hold and by addressing these now, do you think that running future studies whether in MMA or other indications, it could be more seamless from making some of these changes now but then also understanding what the agency is looking for in IND packages on CMC?
There are indications that could be more seamless from making some of these changes now, but then also understanding what the agency is looking for a 90 packages on CMC.
Speaker Change: Yeah, good question, Kristen. So we haven't disclosed the exact nature of the questions, but I think I've been clear in the past, they were all around the AEV capsid, MMA 101. They had questions around additional analytics.
Yes, good question Kristen.
So we haven't disclosed the exact nature of the questions, but I think I've been clear in the past.
We're all around the AAV capsid and then they have 101.
They had questions around additional analytics.
Speaker Change: which usually have been asked more in a phase three setting, but as you said, I think it's great we got this out of the way early before we even started the trial. And just to give you one specific example.
Which usually have been asked more in our phase III setting, but as you said I think it's great and get us out of the way early.
We even started the trial.
And just give you one specific example.
Speaker Change: The FDA is looking at the ratio of empty to full capsule, for example. I mean, that's one very specific question. So, we completed all the analytical work and then, you know, supplied the answers, provided the answers on February 9th. And then.
The FDA is looking at the ratio.
Of empty to full capsid for example, I may ask one very specific question. So.
We completed all the analytical work and then.
Supplied the answers provided the answers on February 9th and then.
Speaker Change: I got the wonderful news yesterday to move forward into the clinic.
Got the wonderful news yesterday.
To move forward into the clinic and.
Speaker Change: And there's definitely learnings for us, but also for our partners as well. I think it's important that we have a clear clinical path with three monthly doses.
And Theres definitely learnings for us.
For for US, but also for our partners as well I think it's important that we have a clear clinical path.
With three monthly doses.
Speaker Change: you know, in kids actually. So I think that provides a lot of certainty for our partners as well. There's a clear regulatory path for Intour in gene therapy.
In kids actually so I think that provides a lot of certainty for our partners as well, there's a clear regulatory path for <unk> in gene therapy.
Speaker Change: Got it. Thanks. And recently, the FDA published a draft guidance on immunogenicity information for therapeutics, including a focus on anti-drug antibody formation and thoughts about how they should be labeled and communicated. So obviously, this phenomenon isn't new across biologics, but curious to hear your thoughts on how some of these criteria across the labeling might impact physician behavior, especially if alternatives come to the market, including with your mTOR technology.
Got it thanks, and recently the FDA published a draft guidance on Immunogenicity information for therapeutics, including a focus on anti drug antibody formation and thoughts about how they should be labeled and communicated. So obviously this phenomenon isn't new across biologics, but curious.
To hear your thoughts on how some of these criteria of cross labeling my impact physician behavior, especially if alternatives come to the market, including with your <unk> technology.
Speaker Change: Yeah, it's not a great question. And, you know, obviously, the FDA has been focused on.
Yes, that's another great question and obviously the FDA has been focused on.
Speaker Change: ADA mitigation for quite a while, and I think the most recent guidance even puts, you know, more emphasis on the importance of ADA mitigation, and I think, you know, to our knowledge, we're the only company, actually, with clinical-stage assets that specifically address ADAs.
80, a mitigation for quite a while and I think the most recent guidance even puts more emphasis on the importance of Adi mitigation.
And I think two arent to our knowledge, we're the only company actually with clinical stage asset that specifically address 80 ace.
Speaker Change: And I think we have demonstrated now across a number of modalities, you know, and obviously most advanced with our gout asset where we recently published a phase one data where we clearly, you know, address ADAs.
And I think we have demonstrated now across a number of modalities.
Obviously, most advanced with our gout asset, where we recently published the phase one data.
Where we clearly.
Yes, 80 A's.
Speaker Change: And with a very immunogenic enzyme, the get-to-case, you pretty much have ADAs in 100% of patients if you don't add Intor. So we're extremely encouraged by this.
And with a very immunogenic enzyme the Gatwick case, you pretty much have 88, and 100% of patients if we don't add into <unk>.
So we're extremely encouraged by this and.
Speaker Change: I think this will foster even more interest in our platform because it can help overcome the challenge of many of the biologics who all have, to some degree, induced ADAs, which impacts efficacy and, more importantly maybe, patient safety.
I think it will foster even more interest in our platform because it can help overcome the.
<unk> of many of the biologics, who all have to some degree.
<unk> 88, which impacts.
And more importantly, maybe patient safety.
Speaker Change: Thank you. And you're clearly very excited about the data you've seen for mTOR-IL and the potential broad applicability. So how are you thinking about integrating this into your current pipeline, including some of these earlier stage programs, versus looking at newer indications and targets?
Thank you and you are clearly very excited about the data you've seen for <unk> IOL in the potential broad applicability. So how are you thinking about integrating this into your current pipeline, including some of these earlier stage programs versus looking at newer indications.
<unk>.
Speaker Change: Yes, we're definitely very excited about Intel IL. We really think that's a generation lead for us. There's excitement around the T-Rex selective IL-2s alone already. The IL-2s basically expand pre-existing T-Rex.
Yes, Yeah, we're definitely very excited about <unk>, we just.
Thing, that's a generational leap for us.
And you know.
There is excitement around.
The T Rex selective IL twos.
Known already.
<unk>.
I'll choose basically expand.
Preexisting T Rex.
Speaker Change: but don't address the anti-synthetic T-rex. Versus IMTOR alone induces anti-synthetic T-rex but not necessarily expand. And the combination, really, we saw highly synthetic effects where we both induce and expand anti-synthetic T-rex.
But don't address.
<unk> and specific T Rex.
Inter alone induces <unk> T Rex, but I'm going to sort of expand into combination.
Really we saw highly synergistic effects, where we both in views.
And expand anesthetic T Rex.
Speaker Change: which is really an amazing evolution of the platform. We see the application really across all three pillars of the pipeline. We've shown some data in a preclinical model of AV gene therapy. We saw very good control of losing the enderbody.
<unk>, which is really an amazing evolution off the platform.
We see the application really across all three pillars of the pipeline.
Joan some data in a preclinical model of AAV gene therapy, we saw.
Very good control of losing antibodies actually at a quarter off the dose of <unk>, which is I think bearing charging as well so thats potential for this combination to be dose sparing.
Speaker Change: actually at a quarter of the dose of mTOR, which is, I think, very encouraging as well. So, that's potential for this combination to be dose-sparing, but we're extremely excited about the application in autoimmunity.
But we're extremely excited about the application in autoimmune disease.
Speaker Change: as, you know, anti-immune tolerance is kind of the holy grail, if you like. And with our approach, you know, we're trying to reimagine immunotherapy for autoimmune disease. Obviously, we've just released this exciting data around JP Morgan's conference and we're in the process
As you know ancillary immune tolerance is kind of the Holy Grail, if you like.
With our approach.
And to re imagine immunotherapy for autoimmune disease.
Obviously, we've just released this exciting data around to JP Morgan.
Conference and we're in the process.
Speaker Change: to identify target indications, but you see us focus a lot more on the autoimmune disease space, based on this exciting data.
<unk> target indications.
But do you see us focus a lot more on the autoimmune disease space.
Based on this exciting data.
Thank you again.
Thanks Kristen.
Speaker Change: Our next question will come from John Neumann with Canaccord. Please go ahead.
Our next question will come from John Newman with Canaccord. Please go ahead.
John Neumann: Hi gentlemen, thanks for taking my question and congrats on the progress. I have a specific question regarding the
Hi, gentlemen, thanks for taking my question and congrats on the progress.
Specific question regarding the.
Speaker Change: potential design for the SEL-302 study in MMA. I know that that study will be initiated later this year, but I wondered if you could just talk to us about some of the potential
Potential design for the <unk> 302 study in MMA, I know, but that study.
We will be initiated later this year, but I wondered if you could just talk to us about.
Some of the potential aspects of that design rigs.
Speaker Change: that design regarding things like frequency of mTOR dosing, et cetera, just whatever you want.
Regarding things like frequency of in toward dosing et cetera, just wherever you might be able to share. Thank you.
Speaker Change: Yeah, thanks for the question. I'll hand this to Peter our CMO.
Yeah. Thanks, Thanks for the question I'll hand, this to Peter our CFO .
Speaker Change: Yeah. Hi. This is Peter Traber, and thanks, John , for that question. I, you know, with the agreement of the FDA that the clinical trial proceed, I think we can now provide some details regarding the MMA clinical trial. Just as background, as we've stated previously, the trial will be conducted at the NIH by Dr. Chuck Venditti, a leading investigator with the largest MMA population in the United States.
Yeah, Hi, this is Peter Traber, and thanks, John for that question.
With the agreement of the FDA on the clinical trial proceed I think we can now provide some details regarding the MMA clinical trial.
Just just as background as we've stated previously the trial will be conducted.
I H by Dr Chuck and duty.
Leading investigator with largest MMA population in the United States.
Speaker Change: The trial will be conducted in cohorts of patients starting with adolescence, age,
The trial will be conducted in cohorts of patients starting with adolescence page 12 through 18, and then progressing to children ages two through 12.
Speaker Change: 12 through 18 and then progressing to children ages 2 through 12.
Speaker Change: The AV8 gene vector carrying the mute gene replacement designated MMA101.
The AAV <unk> gene vector carrying the gene replacement designated MMA 101 will be administered at a dose of <unk>.
Speaker Change: will be administered at a dose of 1E13 viral genomes per kilogram. This is a dose which has been shown to have excellent efficacy in non-clinical animal models, and we expect this dose to have therapeutic efficacy in humans. The dose of.
One E 13 viral genomes per kilogram. This is a dose which has been shown to have excellent efficacy and non clinical animal models and we expect this dose to have therapeutic efficacy in humans.
The dose of <unk>.
And then maybe one on one.
Speaker Change: will be given with three doses of mTOR to potentially prevent the development of antibodies.
We'll be given with three doses of <unk> to potentially prevent the development of antibodies, which might allow future re dosing mitigate hepatic toxicity associated with gene therapy and enhance the first dose effect of gene therapy.
Speaker Change: which might allow future redosing, mitigate hepatic toxicity associated with gene therapy, and enhance the first dose effect of gene therapy, as Karsten had mentioned.
Carsten had mentioned.
Speaker Change: The first dose of mTOR will be administered at the time of the gene therapy administration, and then doses 2 and 3 will be given on day 28 and day 56 following the MMA 101 administration.
The first dose of them tour will be administered at the time of the gene therapy administration, and then doses two and three will be given on day 28 and day 56, following the MMA one O one administration.
Speaker Change: There are provisions in the protocol for dose escalation of mTOR depending on the effect on anti-AV8 antibody production. And there will be an adolescent subject treated without mTOR for comparison with that patient will get steroid prophylaxis whereas those.
There are provisions in the protocol for dose escalation of <unk>, depending on the effect on an anti <unk> antibody production.
There will be an adolescent subject treated without them tour for comparison.
With.
That patient will get steroid prophylaxis, whereas those.
Speaker Change: treated with mTOR will not have steroid prophylaxis, as that's not a relative contraindication in subjects with MMA.
Treated within tour will not have steroid prophylaxis.
Relative contra indications in subjects with MMA.
Speaker Change: Each subject will be treated sequentially with the assessment of safety and efficacy by a data safety monitoring board at three months following the infusion of the gene therapy.
Each subject will be treated sequentially.
With the assessment of safety and efficacy by.
Data safety monitoring board.
Three months following the infusion of the gene therapy.
Speaker Change: before progressing to the next patient. The adolescents will be treated, three adolescents will be treated, followed by three children with a dose of 1E13. The primary efficacy measures will be done at three months, and they'll be serum methylmalonic acid levels, C13 propionic breath test, which is a direct measurement of enzymatic activity.
Before progressing to the next patient.
The adolescents will be treated.
<unk> license will be treated followed by three children.
With a dose of one <unk>.
The primary efficacy measures will be gun at three months and there'll be serum metal Milan of gas with levels.
See 13, propionic <unk> breath test, which is a direct measurement of enzymatic activity.
Speaker Change: as well as clinical status, including episodes of decompensation and dietary prescription. In addition, the primary immunologic endpoint will be the development of neutralizing antibodies to AAV8 to assess the effect of mTOR. Following enrollment and assessment of the six treated subjects, three adolescents and three children
As well as clinical status, including episodes of the compensation and dietary prescription.
Addition, the primary immunologic end point will be the development of neutralizing antibodies to AAV eight to assess the.
Effective inventory.
Following enrollment and assessment of the six treated subjects three adolescents with three children.
Speaker Change: We will hold discussions with the FDA to determine whether to continue the program with the 1E13 dose of MMA 101 or to consider dose escalation or even potentially de-escalation.
We will hold discussions with the FDA to determine whether to continue the program with the $1 13 dose of MMA, one on one or to consider.
Dose escalation or even potentially D escalation.
Speaker Change: And as Karsten mentioned, now with the program off clinical hold, we anticipate infusing the first subject in the trial in the second half of this year.
And as Carsten mentioned now with the program off clinical hold.
Anticipate infusing the first subject in the trial in the second half of this year.
Speaker Change: So, John , those are some details of the trial. Happy to answer any questions regarding that.
So John those are some details of the trial happy to answer any questions regarding that.
John Neumann: Oh, great. Thank you. That's a lot of detail. It's really helpful. The only follow-up I had was just curious how long you'll be able to follow patients.
Great. Thank you that's a lot of detail its really helpful.
The only follow up I had was just curious.
How long you'll be able to follow patients in the.
The study.
Speaker Change: Yes. So, the initial assessment of efficacy and safety will be, as I mentioned, at three months. But the study will follow closely the subjects for a full year. And then
Yes so.
The initial assessment of efficacy and safety will be as I mentioned, the three months, but the study will follow closely the subjects for a full year and then.
Speaker Change: intermittent follow-up over the next four years. So we will follow the subjects for at least five years following the dosing.
Intermittent follow up over the next four years. So we will follow the subjects for at least five years following the boot dosing.
Excellent. Thank you.
Speaker Change: Our next question will come from Raju Prasad with William Blair. Please go ahead. Thanks.
Our next question will come from Rajiv Prasad with William Blair. Please go ahead.
Thanks for taking the question.
Raju Prasad: On the phase one trial for 399, did you mention the potential to redose and how will that determine?
On the on the Phase one trial for 309 did.
Did you mentioned the potential to re dose and Ho Hum.
How would that determination be made.
Speaker Change: Yeah, I, Carson, I can answer that if you'd like. It's a very good question. Redosing of gene therapy or dosing of gene therapy is
Yeah.
Kirsten I can answer that if you'd like.
It's a very good question.
Re dosing of gene therapy, we're dosing of gene therapy is primarily related to whether there are neutralizing antibodies.
Carson Brun: primarily related to whether there are neutralizing antibodies present. So anywhere from, from 20 to 50% of people.
So anywhere from from 20% to 50% of people have neutralizing antibodies to AAV and they're generally not eligible for for gene therapy. So we have our guidance so.
Carson Brun: have neutralizing antibodies to AAV, and they're generally not eligible for gene therapy. So we have a guidance. So redosing, eligibility for redosing would be based on the level of neutralizing antibodies at the time when redosing was gonna be done.
Re dosing the eligibility for re dosing would be would.
It would be based on.
The level of neutralizing antibodies at the time when re dosing was going to be done and.
Carson Brun: And we think that that's a regulatory endpoint which will be defensible.
And we think that that's a regulatory endpoint, which will be defensible.
Carson Brun: The, in the 399 study.
The.
In the 399 study.
Carson Brun: With the 0.3 mg per kg dose, we had antibodies at 30 days that were at the level that would allow redose.
With the 0.3 Meg per kg dose we had.
Antibodies.
30 days that were at the level that we.
Would allow re dosing.
Carson Brun: By 90 days, as you'll recall, the neutralizing antibody levels rose.
By 90 days as Youll recall.
The neutralizing antibody levels rose.
Carson Brun: And that's the same thing we have found in animal studies. In animal studies, when we gave three doses of mTOR, we were able to suppress antibody production at 90 days and beyond.
And that's the same thing we have found in animal studies.
In animal studies, when we gave three doses of them tours, we were able to.
Suppress antibody production at 90 days and beyond and.
Carson Brun: And so that's why we think that giving three doses of mTOR will allow us to suppress antibodies long-term, and it's, you know, why the FDA agreed that we should give three doses of mTOR in the MMA trial.
And so that's why we think that giving three doses.
M M tour will allow us to suppress antibodies long term.
And it's why the FDA agreed that we should give three doses.
Tore in the MMA trial.
Speaker Change: I don't know if that answers your question, Roger, if you have a follow-up.
I don't know if that answers your question Roger if you have a follow up.
Roger: Yeah, no, that's helpful. Is there a plan to go any to ages below two years in the trial at any point? Obviously, another M&A program is put on clinical hold for TMA and two cases of TMA in younger patients. But I was just kind of curious to hear your thoughts there as well.
Yeah, No that's helpful.
Is there a plan to go any ages below two years two years in the trial and at any point obviously.
Hey, another MMA program was put on clinical hold for her TMA in two cases with TMA in younger patients. So I was just kind of curious to hear your thought.
That's there as well.
Speaker Change: Yes, that's also a very good observation. We know that as the adverse effect profile gets filled out both for gene therapies as well as particular indications, so each gene therapy is not just related to the vector that's given. It's also the underlying disease.
Yes.
That's also a very good observation.
We know that.
As the as the.
Adverse effect profile.
Gets filled out both for gene therapies as well as particular indications. So each gene therapy is not just related to the vector that's given its also the underlying disease and of course <unk>.
Speaker Change: And, of course, given the two cases that Logic Bio announced of TMA,
Given the two places.
But logic bio.
Yeah.
<unk> the PMA.
Speaker Change: That's very concerning, and it's why we're taking the approach of
It's very concerning and it's why we're taking the approach.
Speaker Change: treating first adolescents, then children, and then, of course, in the future, the goal would be to extend therapy to children less than two years old, but by that time, we'll have a lot more data on the...
Treating adolescence than children and then of course.
In the future the goal would be to extend therapy to children less than two years old but by that time, we'll have a lot more data on the.
Speaker Change: the efficacy and safety of our dosing.
The efficacy.
And safety of our of our dosing the other thing is.
Speaker Change: The other thing is, you know, our dose of AV8 is lower than Logic Bio and what we've seen.
Our dose.
The VA there is lower than logic bio and what we've seen so far with both hepatic toxicity as well as TMA that its the higher doses of gene therapy approaching or going over one <unk> 14, which is the log higher than we're starting.
Speaker Change: so far with both hepatotoxicity as well as TMA, that it's the higher doses of gene therapy, you know, approaching or going over 1E14, which is a log higher than what we're starting, is where most of the problems have been, the major problems have been seen.
Where most of the problems have been.
The major problems have been seen.
Speaker Change: Great, thanks, Peter. And then you mentioned, Karsten, in the prepared comments and the press release on the Dissolve 2 trial being kind of impacted by the conflict in Russia, or sorry, in Ukraine.
Great. Thanks, Peter and then.
You mentioned Carson in the prepared comments in the press release on the resolve II trial being kind of impacted by the conflict in Russia.
Starting in Ukraine.
But how many patients and the dissolved one trial were enrolled at those sites.
Speaker Change: How many patients in the Dissolve One trial, you know, were enrolled at those sites? And, you know, are there any potential complications on follow-up there? Just kind of curious to hear the impact kind of to the program overall. Thanks.
Are there any potential complications on follow up there just kind of curious to hear the impact coming through the program overall thanks.
Speaker Change: Yeah, Ross, that's a great question, and I'm gonna give that to Peter. He's gonna get all the difficult questions today. Yeah, thank you. Yeah, that's a very good question. And just to review, the Dissolve I and II trials are identical Phase III trials with a primary endpoint at six months. The only difference between the two is that Dissolve I has a six-month treatment extension period
Yeah, that's a great question and I'm going to give that to Peter who is going to get all the difficult questions today.
[laughter] yeah. Thank you, yes, that's a very good question and just to review.
The dissolved one and two trials are identical phase III trials with a primary endpoint at six months. The only difference between the two is the dissolved one hasnt six months.
Extension treatment extension period.
Peter: of the total treatment period is 12 months. The Dissolve One study is US only.
Total treatment period is 12 months the dissolved one study is U S only.
Peter: and enrolled, already completed enrollment, as Karsten mentioned, of 112 subjects by November , last November , and we will have top-line data by the end of the year. So there's nothing in the Russia-Ukraine situation that will affect the completion of subjects in the Dissolve I trial.
<unk> enrolled already completed enrollment at as Carsten mentioned of 112 subjects by November last November and we will have top line data by the end of the year. So there is nothing in the Russia Ukraine.
Crane.
Situation that will affect the completion of subjects in the dissolve one trial.
Peter: The Dissolve 2 trial, which has not yet completed enrollment, but still has a six-month endpoint, has several European sites, including Russia and Ukraine.
The dissolved true two trial, which is not yet completed enrollment, but still has a six month <unk>.
Endpoint has several European sites, including Russia and Ukraine.
Peter: The disruption of our clinical programs, of course, due to the Russian invasion is an industry-wide problem. Our main issues have been operations disruptions, such as the supply of
The disruption of our clinical programs of course.
Due to the Russian invasion.
Industry wide problem, our main issues have been operations disruptions such as the supply of resupply of drugs and other supplies the lack of in country personnel illuminate communication.
Peter: resupply of drugs and other supplies, the lack of in-country personnel, limited communication, payment uncertainty, and interruption of patient visits. And we're closely working with our CRO Paracel to address and while maintaining the safety of the personnel and patients.
Payment uncertainty an interruption of patient visits.
And we are closely working with our CRO paired so to address and while maintaining the safety of our personnel and patients.
Peter: We have four active sites in Russia and three active sites in Ukraine, representing about 12% of the total number of sites in our study. And that's kind of representative of many other companies' clinical trials.
We have four active sites in Russia, and three active sites in Ukraine.
Representing about 12% the total number of sites in our study and Thats kind of representative of many other companies clinical trials.
Peter: We've temporarily closed the...
We've temporarily.
Closed the.
Peter: the Russian and Ukrainian sites to patient screening and enrollment of new patients so that we can focus on conserving resources and supplies to complete the already enrolled subject.
The Russian and Ukrainian sites to patient screening and enrollment of new patients. So that we can focus on conserving resources and supplies to complete the already enrolled subjects.
Peter: And given the very fluid situation, at this time we don't have an estimate of what percentages or numbers of subjects we'll be able to complete.
And given the very fluid situation at this time, we don't have an estimate of what percentages or numbers of subjects will be able to complete.
Peter: We have undertaken a couple of really key mitigation measures. As Karsten mentioned, we've added 11 study sites to the dissolved trial, all in the United States.
We have undertaken a couple of really key mitigation measures as Carsten mentioned we've added.
<unk> study sites to the dissolved trial all in the United States.
Peter: And nine of those have already been activated, and the final two will be activated this month. And second, we've requested a meeting with the FDA to discuss the statistical handling of subjects enrolled in Russia and Ukraine.
Nine of those have already been activated in the final two will be activated this month.
And second we've requested a meeting with the FDA to discuss the statistical handling of subjects enrolled in Russia, and Ukraine should they not be able to complete the study due to the war.
Peter: should they not be able to complete the study due to the war. This will be important to our understanding whether additional subjects need to be enrolled in the trial to maintain study power and so forth. So,
This will be important to our understanding whether additional subjects needed to be enrolled in the trial to maintain study power and so forth. So.
Peter: While our guidance right now is top-line data for Dissolve-2 in addition to Dissolve-1 by the end of the year, we continue to assess, you know, our continued assessment of the status of the enrolled subjects in Russia and Ukraine, our consultation with the FDA.
While our guidance right now is topline data for dissolved two in addition to dissolve one by the end of the year. We continue to assess our continued assessment of the status of the enrolled subjects in Russia, and Ukraine or a consultation with the FDA.
Peter: and the performance of our newly added sites will be monitored and we'll update guidance as the situation is clarified. At the present time, it's a little hard to project while we have all these different moving parts.
And the performance of our newly added sites will be monitored and we will update guidance as the situation has clarified at the present time, it's a little hard to project, while we have all these different moving parts.
Thanks.
Speaker Change: Our next question will come from Gil Bloom with Needham, please go ahead.
Our next question will come from Gil Blum with Needham. Please go ahead.
Speaker Change: Hey, this is Chen for Gail. Thank you for taking our question. I just want to ask if you have observed any developed immunity against the PagChain in mTOR previously?
Hey, this is Chen for Gail Thank you for taking our question.
I just wanted to ask if you have observed.
Default the immunity against the powertrain and tour previously.
Speaker Change: Generated immunity to what? I'm sorry.
Okay.
Generated immunity to what I'm sorry.
Chen: Oh, generated immunity against the PagChain in TOR.
Oh generated immunity against the pathogen.
EMCORE.
The packaging is that we.
The Pac 10 Pega Chen.
In our particles.
Speaker Change: I'm not sure. Oh, Paul, sorry. Paul, I have a phone call. Ken's in the party. Thank you, Mason.
I'm not sure Paul.
Sorry.
Paul I ask on the panel tests.
Nation.
Yes.
Speaker Change: Yeah, because there is percolation in a particle, so is there any developed immunity against that? Ah, yes.
Yes.
There was speculation part of Buffalo.
So is there any developer immunity against that.
Yes, okay.
Speaker Change: Yeah, that's a good question, because there is PEG in the attached to the mTOR particle, and
Yeah. That's a good question because there is pegged in the.
Types of inventory particle.
And.
Speaker Change: No, we have not identified specific antibody generation against the nanoparticle-associated PEG.
No we have not.
<unk> identified specific.
Antibody generation against the.
Nanoparticle associated pig.
Speaker Change: Now, there is the enzyme, pegadracase, is also heavily pegylated.
Either there is.
The enzyme to gather cases also heavily pegylated.
Speaker Change: But the antibodies that we've seen that have been generated through Gagrecase is more to the protein epitope rather than the pegylation. With Christexa, Peglodicase, that uricase, the antibodies have been generated to the pegylated portion, but that's not what we've seen with Pegadricase.
Both the antibodies that we have seen that have been generated to aggregate more to the protein epitope rather than the pegylation.
With with KRYSTEXXA.
Pegloticase.
Your case, the antibodies have been generated to the Pegylate a portion, but that's not what we've seen with big aggregates.
Thank you.
Sure.
Speaker Change: Our next question will come from Yun Zhang with BTIG. Please go ahead.
Our next question will come from young Zhang with BTG. Please go ahead.
Yun Zhang: Hi, thank you for taking the question. So the first one is on MMA program. Can you remind us the origin of the MMA 101 capsule? Was it derived from some type of wild-type capsule, please?
Hi, Thank you for taking the questions. So the first one is on MMA program can you remind us the origin of the MMA. One O. One capsule was it derived from some type of wild type cuts that please.
Speaker Change: Yeah, yes, it's an A-E-A capsule.
Yes, yes, it's an H D a.
Yeah.
Speaker Change: So, yeah, just to kind of follow up on the TMA observation from another study, I know that you're in combination with mTOR to deal with the immunogenicity, but any lessons that you can potentially learn from that observation, and do you think you have sufficient mitigation already incorporated in the study to prevent any potential immunogenicity?
Okay. That's it okay. So yeah just.
Kind of follow up.
TMA observation from another study I know that sure.
In combination was aimed towards true tier was the immunogenicity, but any lessons that you can potentially to learn from that observation and do you think you have sufficient mitigation already incorporated in the study to prevent any.
Potentials.
Genesis related side effects.
Speaker Change: Yeah, obviously we were building on the learnings that we have, you know, within TOR and, you know, one of the...
Yes, obviously, we're building on the learnings that we have.
With them tour and one of the potential benefits is that we are.
Speaker Change: potential benefits is that, you know, we're addressing the immunogenicity of the AAV capsid. But, you know, we have extensive experience within TOR in the GOU trial where we've demonstrated we prevent the formation of ADAs, and then we have, you know, indication from the 399 trial, the empty capsid, that we prevent the formation of NAPs, and that's really what we're building on.
We're addressing the immunogenicity off of the AAV capsid so.
But.
We have extensive experience within tour in.
Indigo trial, where <unk> demonstrated we prevent the formation of <unk> 88, and we have indications from.
The 309 trial the empty capsid that we prevent the formation of Naps and that's really what we're building on.
Speaker Change: our assumption and that's how we discussed with the FDA and they're, you know, they were comfortable that this is a, you know, very interesting approach which could be, you know, actually transformational for the field if we're able to prevent the formation of NAPs.
Our assumption and that's how we discussed with the FDA and they were comfortable.
This is a.
Very interesting approach, which could be actually transformational for the field.
We're able to prevent the formation of naps and ultimately re dose.
Speaker Change: and ultimately redose and, you know, address many of the secondary issues, you know, such as the high doses and toxicity associated with the high doses. And, you know, we've also demonstrated in, at least in animal models that.
Address many of the secondary issues, such as the high doses and toxicity associated with the high doses.
And we've also demonstrated.
At least in animal models that.
Speaker Change: IMTER also has hepatoprotective properties as well, probably related to autophagy, but obviously we'll have to see in the actual trial, but we feel comfortable that we, and the FDA, most importantly, is comfortable that we have a safe setup here.
<unk> also has hepatic protective properties as well.
Probably related to Autophagy.
But obviously, we'll have to see in the actual trial, but we feel comfortable that.
<unk>.
The FDA most important these comfortable that we have set.
Set up here.
Speaker Change: Okay, so with the decision to de-prioritize OTC deficiency program, does that mean that in the long term enzymatic therapy and also autoimmune disease could?
Okay. So with the decision to de prioritize OTC deficiency program does that mean that in the long term.
Enzymatic therapy, and also autoimmune diseases potentially be more interesting.
Speaker Change: more interesting or more promising direction for the company and did you say that the combination of mTOR and io12 sorry io2 and
More promising direction for the company and did you say that the.
The combination of important IL 12, sorry, I O two and.
The combination also has activity in.
Speaker Change: The combination also has activity or potential use in gene therapy as well.
Or potential using gene therapy as well.
Speaker Change: Yeah, so I think pausing the OTC program is really, you know, giving the market backdrop, we're very cautious on how we spend our money.
Yes, so I think.
Pausing the OTC program.
Really you know given the market backdrop, we're very cautious in how we spend our money.
Speaker Change: We're not saying we're discontinuing the program, we're pausing it for now, which leads to obviously cost savings.
We're not saying we're discontinuing the program we're pausing for now.
Which leads to obviously cost cost savings and we put our efforts behind the MMA program. This is not an indication that we're less excited about gene therapy.
Speaker Change: We put our efforts behind the MMA program. This is not an indication that we're less excited about the gene therapy, but we think
Speaker Change: The deployment of capital is the most efficient in focusing on the MMA program for now.
I think the deployment of capital is.
The most efficient and focusing on the MMA program for now.
Speaker Change: We obviously also have a number of partnerships, you know, growing partnerships, most recently with Takeda. So, we see a lot of, you know, potential use of mTOR in gene therapy, not only mTOR but also with SORG. And you're right, we have generated, you know, very compelling data.
We obviously also have a number of partnerships.
Growing partnerships most recently with Takeda So we see a lot of potential use of <unk> in gene therapy.
Not only <unk>, but also with the <unk>.
And you're right we have generated.
Very compelling data.
Speaker Change: with IMTOR-IL, so the combination of IMTOR with an IL-2 receptor.
With <unk>, so the combination of <unk> with an IL two.
Receptor agonist.
Speaker Change: in a mouse model of AV gene therapy where we demonstrated basically complete control of NAVs after two AV doses at a quarter of the dose of mTOR, so you know, which would usually be a sub-therapeutic dose. So we definitely see application also in gene therapy down the line.
In a mouse model of AAV gene therapy, where we demonstrate it basically complete control of nabs after two AAV doses at <unk>.
Quarter after dose of aim tour.
No.
Which would usually be a sub therapeutic dose. So we definitely see application also in gene therapy down the line.
Okay, great. Thank you very much.
Thank you Ian.
Speaker Change: Our next question comes from Uyir with Mizuho. Please go ahead.
Our next question comes from <unk> with Mizuho. Please go ahead.
Uyir: Hey guys, thanks for taking my question. Just going back to the trial design for SEL 302.
Hey, guys. Thanks for taking my question.
Just going back to the trial design for <unk> L. S.
L three O two.
Uyir: I wasn't sure if I heard correctly, is there any, in the protocol, is there...
Hi.
I wasn't sure if I heard correctly is there any.
And the protocol is there.
Uyir: Anything for re-dosing at the, I guess, at the end of the first three months if patients, if you don't see efficacy in the patient?
Anything for re dosing at the I guess at the end of the first three months.
Some patients have you don't see efficacy in the patients.
Speaker Change: Yes, no, there in this protocol, there's no provision for redosing during the first three months or within a year.
Yes, no there.
This protocol there is no provision for re dosing.
During the first three months or.
Within a year.
Speaker Change: Redosing is going to depend on the level of efficacy of the gene therapy and how long it lasts and so forth.
Re dosing is going to depend on the level of efficacy of the <unk>.
Gene therapy, and how long it lasts and so forth.
Speaker Change: We, the FDA was very interested in that possibility and opened the door for us coming back to them at any point in time if we see results that would allow redosing. But there's nothing in the protocol.
Hum.
The FDA was very interested in that possibility and open the door for us coming back to them at any point in time if we.
<unk> results that would.
Allow re dosing, but there is nothing in the protocol.
Speaker Change: Okay, so even after three months, after the assessment, I guess what you seem to be saying
Okay. So even after three months.
After the assessment on doesn't.
So what did you seem to be saying is that you.
Speaker Change: could go back to the FDA and re-treat the patients, is that correct?
Could go back to the FDA and re treat the patients is that correct.
Speaker Change: Yes, so in our discussions with the FDA, they left that open for us to return and talk to them about that. They didn't want to approve that a priori, but they were very open for us to come back and discuss that.
Yes, so the.
Discussions with the FDA they left that open for us to return to talk to them about that they didn't want to approve that a priority, but there. They were very open for us to come back and discuss that.
Speaker Change: Okay, thanks. And I guess the second question I have is on TZOLT2. I'm just wondering, like, what was the targeted number of patients that were expected to enroll in Ukraine and Russia? And what...
Okay. Thanks.
And I guess the second question I have is on dissolved two I'm just wondering like what was the.
The targeted number of patients that were expected to enroll in Ukraine, and Russia and what.
Speaker Change: How many patients have been, I guess, treated and have completed treatment?
How many patients have been I guess treated plan have completed treatment.
If you can share.
Speaker Change: Yeah, we haven't disclosed exact numbers of patients per country and or how many were enrolled and so forth. And the situation is quite fluid. We've enrolled a certain number of subjects in Ukraine and Russia. And we're not certain at this point, we will over the next month or so.
Yes, we havent disclosed exact numbers of patients per country.
How many were enrolled and so forth and the situation is quite fluid we've enrolled a certain number of subjects in Ukraine and Russia.
And we're not certain at this point.
We will over the next month or so.
Speaker Change: understand how many of those are going to be complete and invaluable. So, we're not, we haven't disclosed the exact.
Understand how many of those are going to be complete and in value. So.
We're not we haven't disclosed the exact.
Speaker Change: What I will say is that the total number of projected patients for Russia and Ukraine was nearing the capacity that we had initially set up.
What I will say is that the.
Total number.
Projected.
For Russia, and Ukraine was nearing capacity that we had initially set up.
Speaker Change: So we did have a targeted number for those countries as well as other countries and it was reaching that target. So now the key thing is where are each of those subjects in the six month treatment and can we complete them? And that's a very fluid situation.
So we did have.
<unk>.
Our targeted number for those countries as well as other countries. Then it was reaching that target. So now the key thing is where are each of those subjects in the six month treatment and can we complete them and that's a very fluid situation.
With.
Speaker Change: Do you think that, I mean, it's kind of hard to assess now, I guess, as she's indicated, but...
Do you think that.
I mean, it's kind of hard to assess now I guess I shouldn't understate it but.
Speaker Change: Based on the number of patients, I guess, that have completed, do you think that you would need to...
Based on the number of patients I guess that have completed.
And do you.
Do you think that you would need to.
Enroll additional patients.
Speaker Change: in order to not have it meaningfully change your, I guess, your statistics.
In order to not have it meaningfully change your.
Yes, Sheila statistics.
Speaker Change: Yeah, that's what we're in the process of assessing. And the study was highly powered already. And as you know, it's a comparison of treatment versus placebo. And the treatment and placebo has basically a zero.
Yes, that's what we that's what we're in the process of assessing.
The study was highly powered already.
And as you know, it's a comparison of <unk> versus placebo and the treatment.
Placebo, who has basically a zero.
Speaker Change: response rate. So it was high-powered for a straightforward end point.
The response rate.
So it was high powered for a straightforward.
Speaker Change: But nevertheless, that's one of the reasons why we'll be talking to the FDA and trying to see how they would have us consider any subjects that do not complete in Ukraine and Russia and assess whether we change the...
But nevertheless, we're that's one of the reasons why we will be talking to the FDA and trying to see how they would would.
Habits consider any subjects that do not complete.
Crane in Russia.
Whether we change the.
Speaker Change: the target for enrollment. We, you know, the target for enrollment was already increased from 105 to 120 some time ago. And our target right now is still approximately 120.
The target for enrollment.
The target for enrollment was already increase from 105 in 'twenty.
Some time ago.
And our.
Our target right now is still approximately 120.
Speaker Change: Okay, a last question for, I guess, for Kevin. Kevin, yes, could you sort of help us think about the quarterly cadence for the R&D spend? I guess the last two quarters have sort of been in the $20 million and would it be something similar, or do you sort of expect it to grow modestly over the year on a quarter?
Okay.
<unk>.
Last question for I guess for Kevin.
Kevin could you sort of help us think about the quarterly cadence for the R&D spend I guess the last two quarters have sort of been in the 20 millions and would it be something similar or do you sort of expected to grow modestly over the year.
On a quarterly basis.
Kevin Tan: That's a great question. With the reprioritization of our spend, I wouldn't expect it to be markedly different going forward. Obviously, we have paused one program, so we're reprioritizing our spend and trying to optimize our cash resources for the highest-value assets. I think that's probably a fair assumption to support.
That's a great question with the re prioritization of our spend I wouldn't expect it to be markedly different going forward obviously.
We have paused one program so we've re <unk>.
<unk> our spend.
And trying to optimize our cash resources for the.
Highest value assets.
Yes.
I think that that's probably.
Finally, if there are some support.
Okay, alright, thank you so much.
Speaker Change: Again, if you have a question, please press star then 1. Our next question will come from Bhubalan Pachayappan. Please go ahead.
Again, if you have a question. Please press Star then one our next question will come from <unk> <unk>.
Please go ahead.
Hi can you hear me okay.
Yes. Thank you.
Bhubalan Pachayappan: Okay, great. A couple of questions from our end. So firstly, how do you envision the Ginkgo partnership to evolve over the next three to five years and what would be the key indicators for success in this partnership?
Okay, Great a couple of questions from our end. So firstly, how do you envision that ginkgo partnership to evolve over the next three to five years and what will be the key indicators protects us in this partnership.
Speaker Change: Yeah, that's a great question. We have, as you know, two partnerships for two of our pillars. One is around the biologics, where they're working on a second-generation IgA protease, and there's obviously, you know,
Yes, that's a great question.
We have as you know two partnerships.
For two of our pillars, one is around the biologics where they work on a second generation Iga protease.
And that's obviously.
Speaker Change: predefined milestones where they have to deliver certain advancements of the enzyme over time. The same is true for the AEV capsule as well. And obviously the goal is to have clinical candidates as quickly as possible.
Pre defined milestones.
They have to deliver certain.
Advancements of the enzyme overtime. The same is true for the AAV capsid as well and obviously the goal is to have clinical candidates as quickly as possible.
Speaker Change: But overall, as you can tell, the cadence of deals, we're quite excited about the partnership. We're in close collaboration with them on both programs.
And but overall as you can tell.
The cadence of deals we're quite excited about the partnership.
In close collaboration with them on both programs.
Speaker Change: Okay. Helpful. And secondly, do you think there might be opportunities for mTOR to be combined with existing approved gene therapy drugs to make the safety profiles better? If so, which drugs would be most appropriate to assess from a combination regimen perspective?
Okay helpful.
Secondly, do you think that might be opportunities for <unk> to be combined with existing approved gene therapy drugs to make the safety profile is better.
I think would be most appropriate to assess from a combination regimen for expecting.
Speaker Change: Yeah, I mean, that's a great question. And obviously, with our portfolio with both Intour and Zork, we have the opportunity to address some of the unmet needs or some of the key unmet needs out of the marketplace. Obviously, right now, there are a limited number of gene therapies, but I mean, that's definitely a potential approach to leverage, you know, both Zork and Intour in the future.
Yes, I mean, it's a great question and obviously with our portfolio with both <unk>.
We have the opportunity to address.
Some of the unmet needs or some of the key unmet needs out in the marketplace.
Obviously right now there are a limited number of gene therapies, but I mean, that's definitely a potential approach to.
To leverage.
Both <unk> and in towards the future.
Yeah.
Speaker Change: All right. Thanks. Thank you.
Alright. Thanks.
Thank you.
This concludes our question and answer portion of the call.
Speaker Change: I will now turn the call back to Selecto's CEO , Carsten Bruhn, for closing remarks. Carsten.
I will now turn the call back to select the CEO Carsten Brennan for closing remarks Carsten.
Carsten Bruhn: Yeah, thank you, operator, and thank you to everyone who joined us this morning for the numerous questions. Please stay safe and healthy, and this concludes today's call. Thank you.
Yes. Thank you operator, and thank you to everyone who joined US. This morning for the numerous questions. Please stay safe and healthy and this concludes today's call. Thank you.
Carsten Bruhn: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.