Q3 2021 Onconova Therapeutics Inc Earnings Call
[music].
Ladies and gentlemen, thank you for standing by welcome to the onto Nova Therapeutics third quarter 2021 financial results and business update conference call.
At this time all participants are in a listen only mode. Following management's prepared remarks, we will hold a question and answer session.
Asked a question at that time. Please press star followed by one on your Touchtone phone. If anyone has difficulty hearing the conference. Please press star zero for operator assistance and as a reminder, this call is being recorded today 11th of November 2021.
At this time I would like to turn the call over to Avi Oler Senior Vice President of corporate development and General Counsel.
Thank you good afternoon, everyone.
Welcome to all goodness third quarter 2021 financial results and business update conference call earlier. This afternoon, we issued a press release reporting our quarterly financial results and business progress if you have not yet.
It is available in the investors and media section of our website Www dot.
Dot com on today's call, you'll first hear from our President and CEO, Dr. Steve Hofmann, who will give a high level overview on our recent progress and future outlook, our Chief Medical Officer, Dr. Mark Gilbert will then provide a more detailed update on our recent clinical and scientific progress.
Before handing it off to Mark Guerin, our Chief Financial Officer.
You our third quarter financial results. Following these formal remarks, we will then finish the call with a question and answer session before passing the call off to Steve I'd like to remind everyone that statements made by management. During this conference call will include forward looking statements under the Safe Harbor provisions of the private security.
These litigation Reform Act of 1995, which involve risks and uncertainties.
That can cause actual results to differ materially forward looking statements speak only as of the date. They are made as the underlying facts and circumstances may change, except as required by law <unk> disclaims any obligation to update these forward looking statements to reflect future information events or circumstances.
Information on forward looking statements. Please review the disclaimer in today's press release and the risk factors in the company's SEC filings with that it is my pleasure to turn the call over to Steve.
Thank you Amit.
Good afternoon, everyone and thank you for joining us.
And we hope you all remain safe amid an ongoing but improving pandemic here in the U S.
Before we begin we would like to say a very special thanks to a group of very special people.
On this veterans day.
Thank you.
All who serve to keep us safe and risk their own well being.
Doing so.
Thank you so much.
I am pleased to update you on the progress and aren't getting over therapeutics.
Since our last earnings call, we have made progress across our pipeline.
We have achieved key milestones.
Also believe our progress during the third quarter.
Has us on track to.
To achieve additional milestones across our pipeline.
And our lead program evaluate O N 123 300.
We recently renamed whereas the cyclists.
We continue to enroll patients in two complementary.
Page one trials in the U S and in China.
As a reminder.
Whereas the cycle is a novel multi kinase inhibitor.
Targeting CDK four and six and then there's an additional kinases involved in tumor Genesis.
Including our Fi.
Which is reported to be involved in cancer cell survival and the mechanisms of how cancer cells metastasize.
The two phase one trials are reevaluating differ.
Different administrations schemes for neuralgia site glib.
Both of which are based on the administration schemes CDK four six inhibitors.
Already approved to treat hormone receptor positive <unk>.
Two negative.
Metastatic breast cancer.
We plan to use the results of our trials to determine neuralgia site racking.
The dose and we remain on track to do this in the first half of 2022.
Beyond our lead program.
We recently reported encouraging data from.
From the investigator initiated.
Phase one slash two eight trials evaluating <unk>.
In combination with the PD, one checkpoint inhibitor <unk> and <unk>.
Patients with advance K, Ras mutated non small cell lung cancer.
These results, which doctor gilder.
Discuss in greater detail support the potential anti cancer activity.
We go through the Golden that combination.
Differentiate Regal theater.
Other Ras pathway modulators.
Only target a particular K Ras mutation.
And suggests that reach.
Sir you may augment.
Africa C of checkpoint inhibitors.
We believe these findings not only bode well.
With the continued clinical development of <unk>.
<unk> in combination with checkpoint inhibition.
K Ras mutated non small cell lung cancer, but may potentially have broad implications across several high unmet indications such as advanced.
Melanoma.
For those of you who are interested in learning more about these data.
We encourage you to view the replay of a webinar announcing the data which featured expert perspectives from the trial's principal investigator Dr. Raj Swamy.
Mount Sinai Medical Center in New York and Dr. Scott Antonia Professor of Medicine at.
Duke Cancer Institute.
The director of its center for cancer immunotherapy.
This webinar can be found on the events and presentations page about website.
We also continued to make progress in our investigator initiated study.
<unk> V go service and recessive dystrophic, Epidermolysis <unk> or.
Odd D E D.
Complicated right squamous cell carcinoma of the skin.
This is a very rare and tragic condition.
With a high unmet medical need.
R E D.
There'll be fatal.
There are no curative therapies available.
Immune oncology agents, which are the current standard of care with <unk>.
Quamish cell carcinoma have yielded disappointing results.
That's the Gallagher will speak more about the disease and ongoing trial in a few moments.
The progress is made.
Our clinical programs during the third quarter.
Ultimately enabled us to achieve notable milestones and we then strengthened.
Our balance sheet with 21 million in gross proceeds from an equity financing.
Plan to use the proceeds from this financing to support the continued development of our pipeline and to potentially drive its expansion.
In licensing of an additional complementary product candidate.
With that I'll now.
I'll now hand, the call over to Dr. <unk> to provide you with more detail on our critical programs and development strategy.
Mark.
So thank you Steve and thanks, once again to all of you who have joined us today.
I'll begin today with an update on the status of our lead the cyclic program.
Some of you may know <unk>, the cyclic formerly known as O N 123, 300 simultaneously inhibits both the cell cycle and cellular metabolism through CDK and our five respectively.
This differentiates Nebraska cyclic from currently approved CDK, four six inhibitors and positions it as a potential treatment for patients.
Factory or have become resistant.
To these agents.
This may be significant.
CDK four six inhibitors generate more than $6 billion in worldwide sales in 2019 alone.
In vitro, Nebraska cyclic.
Was shown to inhibit the growth of the number of cancer cell lines, including breast cancer that are resistant to power both side club, which is the most widely prescribed CDK four six inhibitor.
No RASM sideslip also inhibits CDK four more potently than powerball cyclic and exhibited improved on target toxicity in in vivo preclinical studies as evidenced by a decrease in neutropenia.
We believe that neurons the cycle potent kinase inhibition profile and potentially improved safety profile may ultimately provide strong anti cancer activity and facilitate continuous daily dosing in patients.
This would provide another important point of differentiation.
<unk>, nor as the cyclical and the currently approved CDK four six inhibitors, such as powerful Sutcliffe and drive upside.
These agents are prescribed in combination with an anti estrogen.
In the three week on.
One quick off treatment schedule due to issues of Tolerability.
Clothing side effects related to neutropenia or low white blood cell counts.
The hope is that in a RASM cyclic safety and efficacy profile will initially positioned as a novel treatment option for CDK four six inhibitor refractory patients.
While also providing them with an opportunity to move first line therapy in the future.
We are evaluating a continuous oral daily dosing schedule and our ongoing phase one study in the U S.
This multi center trial seeks to enroll patients with advanced cancers, including but not limited to hormone receptor positive her two negative metastatic breast cancer, who are refractory to or progressing on currently approved CDK four six.
<unk> inhibitors.
To date, we have completed enrollment in the first cohort.
With 40 milligrams orally once a day.
And are currently enrolling patients in the second cohort at 80 milligrams orally once a day.
In parallel with our U S. Phase one study we are also advancing a phase one study in China in collaboration with our partner panics biopharmaceutical.
This trial is designed to complement our U S study by evaluating a three week on one week off dosing schedule of oral Morasses cycling.
To date the hand next trial is fully enrolled the third dose cohort.
At 120 milligrams orally once a day.
<unk> is currently enrolling.
Fourth dose cohort at 160 milligrams orally once a day.
No cases of grade three or higher neutropenia or other dose limiting toxicities have been seen to date in either trial.
Together, we expect findings from the complementary trials in the U S and China.
<unk> informed our recommended phase two dose and treatment regimen for future trials, including a phase II basket study that will enroll patients with several different types of cancer.
Based on preclinical models, one type of cancer, we intend to enroll includes the hormone receptor positive her two negative metastatic breast cancer patients who are resistant to the approved second generation CDK <unk> inhibitors, we expect.
Spec to initiate this trial in the second half of next year.
Beyond our planned basket study, we also expect the findings.
Our ongoing phase one program to inform the design of one or more additional clinical trials that will evaluate the safety and efficacy of Nebraska cyclic in combination with other anti cancer agents.
Specific plans around these trials are currently under development.
And we will be shared once they have been finalized.
Moving on I'd now like to discuss our investigator initiated programs evaluating Rico searches are Ras pathway modulator, which continues to make exciting progress.
Our last earnings call.
We discussed recently published preclinical data that demonstrated the ability of Greek asserted to synergize with checkpoint inhibitors by reversing the immunosuppressive tumor microenvironment through the Upregulation of novel antigens, such as <unk> 40 <unk>.
Yourself.
In September we then reported very encouraging preliminary clinical data, suggesting that the observed preclinical synergy between Greek assertive in checkpoint inhibition may translate to patients and potentially provide meaningful clinical benefit.
These data from the phase one two way investigator initiated trial evaluated.
In combination with the PD, one checkpoint inhibitor <unk> in patients with advanced K, Ras mutated non small cell lung cancer.
I'll provide a short recap of this encouraging data now which is topical given that November is lung cancer awareness month.
Results from the trials preliminary readout.
That two out of seven Evaluable patients achieved a resist defined partial response with another patient showing stable disease, which gifts objective response and disease control rates of 29% and 43% respectively.
In addition, the study doublet of <unk>, and <unk> was well tolerated and the maximum tolerated dose of the doublet was not reached.
Taking a closer look at the study design and data there.
There are several key points that have generated a high level of enthusiasm from key opinion leaders and would speak to just power encouraging. These initial findings are.
The first point is related to the patient population enrolled in the study.
These patients were extensively pretreated with nine of 12, having failed at least two prior lines of therapy and all enrolled patients failed at least one line of prior therapy with a PD one checkpoint inhibitor.
This is significant as PD one is the target of Navona map, which was administered in combination with <unk>.
Fact that we were able to achieve responses in patients who previously failed.
Therapy targeting the PD, one checkpoint by combining an anti PD one therapy with reasserted provides encouraging evidence of <unk> ability to synergistically combine with checkpoint inhibitors and augment their efficacy and K Ras mutated cancers.
This is important as K Ras mutations are the predominant genetic driver of non small cell lung cancer and there is currently a lack of effect treat them options for these patients who failed to adequately respond to checkpoint inhibitor therapy.
A second key finding from the preliminary data readout that I would like to highlight is related to the underlying varied K Ras mutations of patients achieving a partial response or stable disease, each of which was different.
This speaks to Rico circuit mechanisms of action, which is not specific to a particular K Ras variants such as G 12 see.
This provides an important point of differentiation between Greig asserted and other Ras pathway modulators targeting particular, K Ras variants, such as G 12, C and potentially positions <unk> to be more broadly applicable.
Lastly, I should note that.
<unk> radiographic responses were seen in both the lung or the primary tumor site and at multiple metastatic sites, which are the major cause of death for these patients.
Collectively.
<unk> data from this phase <unk> study together with the preclinical data we discussed on our last earnings call suggests that Rico asserted may synergize with checkpoint inhibition and that Rico Sir.
Checkpoint inhibitor combinations may be applicable not only to K Ras mutated non small cell lung cancer, but two other indications.
Where PD, one or PDL, one inhibitors are the standard of care such as melanoma.
Yeah.
Looking ahead, the phase <unk> non small cell lung cancer trial continues to enroll patients.
As part of the expansion phase.
Highest dose of oral rig a circuit as defined in the protocol.
And the principal investigators intend to complete the trial per protocol and anticipate opening additional excuse me anticipate reporting additional data from this study in 2022 in.
In parallel and additional studies that will allow for further dose escalation is also under consideration.
Since the maximum tolerated dose of the <unk> doublet was not reached in the ongoing trials dose escalation phase which has been completed.
Based on the data from these two trials, we hope to identify the doublet to recommended phase two dose and better inform its clinical development.
Beyond the investigator initiated K Ras mutated non small cell lung cancer trial, we intend to further leverage the immuno therapeutic effects of rig asserted through a separate investigator initiated study evaluating <unk> in combination.
With a PD one checkpoint inhibitor in advanced recurrent malignant melanoma.
This trial is supported by both the encouraging preliminary data from the non small cell lung cancer trial and by the preclinical melanoma studies that were featured in the peer reviewed publication out of Vanderbilt that we discussed on our last call.
We and the investigators are currently finalizing the protocol for this trial will be submitted to the FDA and expect that it will be initiated in the first half of 2022.
Moving on I'd like to speak very briefly about the investigator initiated trial evaluating <unk> monotherapy in advanced squamous cell carcinoma associated with recessive dystrophic Epidermolysis <unk> below <unk>.
Our our D b.
As Steve mentioned this is an ultra rare condition with an extremely high unmet medical need.
It is invariably fatal.
It is caused by a loss of expression of key protein collagen, seven which causes extreme skin fragility and chronic wounds formation.
Over time, many patients develop squamous cell carcinoma with the over expression of polo like kinase, one or <unk> one.
The scientific rationale for the ongoing trial of <unk> in this indication, which was suggested by a leading expert.
On R&D E. B comes from that drug screens that identified <unk> as the most potent inhibitor of polo like kinase, one or P. L. K one test.
We've seen promising evidence of Ricoh certain clinical activity in this indication to date and plan to provide additional updates on the.
The trials data as it matures as well as at a medical meeting.
In the upcoming months.
Finally.
Before handing off the call.
Mark Guerin to talk about our financials I'd like to reemphasize one point.
While we are of course very interested in the outcomes of the ongoing investigator initiated studies and plan to continue evaluating opportunities to potentially initiate additional studies of this nature. We remained committed to preserving our primary focus and resources on neurosis cycling.
We believe this strategy is the best way to ensure the efficient advancement of our lead program, while positioning us to generate value through rig are set to continue development and high unmet need indications.
And with that I'll turn the call over to Mark Guerin for a discussion of our Q3 financial results Mark.
Thanks, Mark and good afternoon, everyone I'll begin with a quick review of our third quarter expenses, and then I'll discuss our cash position and cash runway.
Research and development expenses for the third quarter of 2021 were $1 8 million and this compares with $4 2 million for the third quarter of 2020.
The decrease was primarily related to higher expenses related to the inspire study in the 2020 period.
General and administrative expenses for the third quarter of 2020 about $2 3 million and this compares with $2 1 million for the third quarter of 2020.
The increase was primarily related to expenses for Investor relations proxy solicitation and fees related to our AGM and special meeting by proxy in 2021.
We reported a net loss for the third quarter of 2021 of $3 5 million or <unk> 22 per share on 60 million weighted average shares outstanding.
This compares with a net loss in the third quarter of 2020 of $6 2 million or <unk> <unk> per share on $12 1 million weighted shares outstanding.
Cash and cash equivalents as of September 32021 were $59 4 million versus $19 million as of December 31, 2020.
Our average quarterly operating cash burn in 2021 has been at $4 3 million.
We believe that our cash position will be sufficient to fund our ongoing clinical trials and business operations through the achievement of significant milestones, including pursuing corporate development opportunities and should be sufficient for more than two years.
This completes my financial review I'll now turn the call back to Steve.
I'd like to thank both marks for the thorough review.
Just heard.
In summary.
We have multiple key near term milestones and value drivers ahead of us.
And our lead in their Azure cyclic program.
We expect our phase one studies and <unk>.
Nice states and China to continue progressing and anticipate selecting a.
<unk> phase two dose in the first half of next year.
This would then be followed by the initiation.
All of our phase II basket trial.
The Gal described including indications such as hormone receptor positive <unk> negative metastatic breast cancer.
It can have.
2022.
In Riga assertive investigator initiated program.
We expect to report additional data from the ongoing <unk>.
The Ras mutated non small cell lung cancer trial in 2022.
We also expect an additional investigator initiated studies evaluating <unk> in combination with a PD one inhibitor in advanced melanoma patients to begin in the first half of next year.
Finally, we continue to actively evaluate strategic licensing opportunities to.
To enhance our product portfolio.
As with all of our decisions.
Any decision on this front will be driven by excellent science and the potential for clinical benefit.
The indication.
Unmet medical need.
So with that review of our clinical progress and our financial results.
Like to open the call for questions.
Operator.
Thank you and ladies and gentlemen, if you wish to register for a question for todays question and answer session.
We'll need to press Star then the number one on your telephone.
Question has been answered and you wish to withdraw your request you may do so by pressing the pound key.
If you are using a speakerphone please pick up your handset before entering your request one moment. Please.
Shane.
And our first question is from Dr. Charles you have.
Google Home Securities. Your line is open.
Yes.
Good evening, guys and thanks for taking my question.
Had one on the rest of cyclin E. As you look towards potentially identifying a recommended phase II dose in the first half of next year.
How and when are you guys thinking about disclosing these data and given you're potentially differentiated mechanism of action how would you set expectations about that data. Thanks.
Thanks, Charles and I'll ask Dr. Gelder to take that question Mark.
Yes, so I think that the.
The data will be disclosed initially at a medical meeting.
Of some sort and followed by publication, but.
The data will be disclosed to the medical meeting.
And.
In terms of the second question I think that.
You know we have.
We are currently considering several different buckets or baskets for the basket trial tumor types to evaluate.
And we're continuing to refine that lifts over time based on the Rnase inhibition profile.
That we have with neurons are cycling.
And we'll also be influenced to some degree by hints of activity or different signals that we see during the course of the phase one study.
And then we will.
That information.
Gets further still.
And it becomes a.
<unk> set in stone so to speak then we will make that public but Steve I don't know if you want to comment further.
No I think our usual markers comprehensive of course, we're looking for signals in the phase of an efficacy trial.
And once we create the Buck and trial, which will probably be mono neuralgia cyclic, but we also will be looking at the potential for combinations of neurons cyclin E. B that was an anti estrogen D that was an immuno oncology drug will be considering those.
Broaches as well.
Yeah.
Understood. Thanks for taking my questions.
Thank you Charles.
Thank you and our next question is from Joe and Janice of H C. Wainwright. Your line is open.
Good evening, everyone. This is Matt on for Joe. Thanks for taking our question. So just quickly we were wondering if and maybe what kind of in licensing you guys might be looking at and if any of that could be complementary to some of the current assets you guys are making some pretty great progress in your pipeline.
Amit would you like to.
And so in Matt's question. Please sure sure. Thanks for the question, Matt and were quite excited about our existing programs and the rapid cycle of Morocco started after Gallagher and doctor freshman between them, but they've been a part of over a dozen oncology drug approvals.
I had a better existing programs. So when we look at that adding a complementary program.
Dr. <unk> stated in his remarks, we're looking at what fits best in the portfolio is another shot on goal.
Or are.
Further expanding our pipeline and look forward to updating our progress on that in the future.
Yeah, great. Thanks, Thanks for taking the question.
Thank you and our next question is from Dr. Robert Langer.
Of note those capital your line is open.
Good evening.
Thank you for the great comprehensive summary of the products.
Dr Guilders summary.
Now recycling.
There were some points about the comparison with with palmar cycling.
Could you just clarify the differentiating factors in the different targets that you would discuss just briefly.
I'll add that the gilded you take that and also that to Cosenza. After Mark's comments may want to add to that.
So you can compare it to the CDK four shifts premier agents.
Yes, so if we if we look at.
Northwest is cyclic and we then look at Cabos cycling.
And we look at the in vitro.
Kinase inhibition profiles.
In terms of the inhibition of CDK four.
123, or <unk>, the cyclic is actually a little more potent than is alba.
If we look at CDK six.
No RASM cyclic is less potent than is powerful and this may be.
The.
Maybe.
Underlying pause or may be responsible for the decrease in neutropenia that we have seen.
Clinically.
In the mouse model, when we compared in RASM cyclic.
Oh and 123.
And our book.
We'll have to see how this plays out.
In.
The phase one study the dose escalation study will have to look carefully at the AE profile, our safety profile et cetera.
Right.
There are.
Several other kinases.
That.
Oh, and 123 or more astrocytes glib hits.
That either a powerboat side clip dosing.
It at all or it hits much more weekly or less potently based on the in vitro kinase.
Profiles, but.
And these include things like our five.
With three.
You see the GFR.
Et cetera et cetera. So there are when you look at them side by side there are several kinases that.
We have activity against that Pablo just does not.
So I'm not sure. If this is answered your question or not if not.
Happy to try and expand a little bit further or Steve may want to expand further as well.
Well actually perhaps Steve Cosenza would like to.
Add something based on our preclinical studies to date, Steve do you have anything to add.
Tomorrow.
Comments sure. Thank you that's a great question Robert.
Robert.
The differentiating point based on in vitro data.
Mark or Dr. Gallagher had spoke to previously.
No.
Although the CK forces inhibitors, rather stick with is the most specific.
Paolo cyclic is probably the most specific and then you have added Mr Lim and.
Narrow should go into which are both.
It would be considered multi kinase inhibitor and <unk>.
On side by side testing there are differences among those two especially about apatow cyclical.
And.
We believe she is differentiating points can be found in those targets both for efficacy and for toxicity profiles.
In published data that we have you can see that cell lines treat it with tableau cyclic versus.
<unk> three <unk>.
As we induce April up to us as we inhibit the AK T.
Hum and EMCORE pathways, which are important for tumor cell survival.
These are not done it publicly so we induce a more sort of toxic type of treating tumor cells, whereas palo and rigor.
And abbvie induce more of a sort of a static Adam cyclically also and this is.
Certain constant effect in certain tumor cell lines.
Like a 123 or narrow cyclic and again, we believe these are based on.
Targets, however, amongst the four CDK four six inhibitors, we are the only one that induces inhibits it's.
Not unusual inhibits arc five and arc five is a very interesting target.
No known approved.
<unk> for arc five however, this is a very important.
Target for tumor cell survival, not so much the proliferation of tumor cells.
The survival of tumor cells and the hypoxic conditions. So we believe this is.
It will be very beneficial.
As part of our mechanism of action.
Okay great.
Yeah.
You actually did answer the question I was really interested in how <unk> compares in terms of the targets.
The potency and the breadth of targets with the approved drugs. So thank you very much.
Youre welcome. Thank you.
Thank you and I am showing no further questions in the queue at this time I'd like to turn the call back to the speakers for any closing remarks.
Yes.
Thank you Laurie.
To all our participants today.
Thank you for participating in today's update call.
We look forward to executing on our business plan and to keep you appraised of all of our progress.
We appreciate your continued interest in our programs and your insightful questions.
Thanks, again and have a lovely evening.
Hope to interact with all of you again soon.
Take care.
And ladies and gentleman. Thank you for your participation on today's conference call.
Today's event and you may now disconnect.
Okay.
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Yes.
Okay.
Okay.
Yes.
Okay.
Yes.
[music].
[music].
[music].
[music].
Ladies and gentlemen, thank you for standing by welcome to the <unk> Therapeutics third quarter 2021 financial results and business update conference call.
At this time all participants are in a listen only mode.
Boeing management's prepared remarks, we will hold a question and answer session to ask a question at that time. Please press star followed by one on your Touchtone phone. If anyone has difficulty hearing the conference. Please press star zero for operator assistance as a reminder, this call is being recorded today.
<unk> 11th of November 2021 at.
At this time I would like to turn the call over to Avi Oler Senior Vice President of corporate development and General Counsel.
Thank you good afternoon.
Unit.
Welcome.
Third quarter 2021 financial results and business update conference call earlier. This afternoon, we issued a press release reporting our quarterly financial results and business progress. If you have not yet in this press release. It is available in the investors and media section of our website www.
That often over dot com on today's call, you'll first hear from our president and CEO Dr. Steve.
We will give a high level overview on our recent progress and future outlook, our Chief Medical Officer, Dr. Mark <unk> will then provide a more detailed update on our recent clinical and scientific progress before handing it off to Mark Guerin, Our Chief Financial Officer to review, our third quarter financial results.
Following these formal remarks, we will then finish the call with a question and answer session before passing the call off to Steve I'd like to remind everyone that statements made by management. During this conference call will include forward looking statements under the Safe Harbor provisions of the private Securities Litigation Reform Act of 1009.
Five which involve risks and uncertainties that can cause actual results to differ materially forward looking statements speak only as of the date. They are made as the.
Underlying facts and circumstances may change, except as required by law <unk> disclaims any obligation to update these forward looking statements to reflect future information events or circumstances for more information on forward looking statements. Please review the disclaimer in today's press release and the risk factors in the company's SEC file.
Earnings.
That it is my pleasure to turn the call over to Steve.
Thank you Amit.
Good afternoon, everyone and thank you for joining us.
And we hope you all remaining safe amid an ongoing but improving pandemic here in the U S.
Before we begin we would like to say a very special thanks to a group of very special people.
On this veterans day.
Thank you.
All who serve to keep us safe.
Risk their own well being.
In doing so.
Thank you so much.
I am pleased to update you on the progress and arent going over therapeutics.
Since our last earnings call, we have made progress across our pipeline.
We have achieved key milestones.
We also believe our progress during the third quarter.
Has us on track to.
To achieve additional milestones across our pipeline.
And our lead program evaluate O N 123 300.
Which we recently renamed <unk> Cyclin.
We continue to enroll patients in two complementary.
Phase one trials in the U S and in China.
As a reminder.
<unk> is a novel multi kinase inhibitor.
Targeting CDK four and six and then there's an additional kinases involved in tumor Genesis, including arc five.
Which is reported to be involved in cancer cell survival.
And the mechanisms of how cancerous cells metastasize.
The two phase one trials are evaluating <unk>.
Different administrations schemes for neuralgia cyclic.
Both of which are based on the administration schemes CDK four six inhibitors.
<unk> already approved to treat hormone receptor positive <unk>.
<unk> negative metastatic breast cancer.
We plan to use the results of our trials to determine <unk> science.
It does and we remain on track to do this in the first half of.
2022.
Beyond our lead program <unk>.
Recently reported encouraging data.
From the investigator initiated phase one slash two eight trials.
<unk> negotiated in combination with the PD, one checkpoint inhibitor move all of that.
Patients with advance K, Ras mutated non small cell lung cancer.
These results, which doctor Gilder will discuss in greater detail support the potential anti cancer activity.
We go through the Golden that combination.
Differentiate Regal theater.
All of the Ras pathway modulators that only target a P.
Tequila K Ras mutation.
And suggests that Regal Acervative may augment.
Efficacy of checkpoint inhibitors.
We believe these findings not only bode well for.
For the continued clinical development of <unk>.
<unk> in combination with checkpoint inhibition and K Ras mutated non small cell lung cancer, but may potentially have broad implications across several high unmet indications such as advanced.
Melanoma.
For those of you who are interested in learning more about these data.
Strongly encourage you to view the replay of a webinar announcing the data which featured expert perspectives from the trial's principal investigator Dr. Raj Swamy of the Mount Sinai Medical Center in New York and Dr. Scott and Tony here.
Professor of Medicine at the Duke Cancer Institute, and the director of its center of cancer immunotherapy.
This webinar can be found on the events and presentations page of our website.
We also continued to make progress in our investigator initiated studies evaluating Regal Acervative recessive dystrophic Epidermolysis <unk>.
Or odd D E B Tom.
Complicated by squamous cell carcinoma of the skin.
This is a very rare and tragic condition.
With a high unmet medical need.
R&D E beam is invariably fatal.
There are no curative therapies available and immune oncology agents, which are the current standard of care the squamous cell carcinoma have yielded disappointing results.
That's the Delta will speak more about the disease and ongoing trial in a few moments.
The progress made in our clinical programs during the third quarter ultimately enabled us to achieve notable milestones and we then strengthened our balance sheet with 21 million in gross proceeds from an equity financing.
We plan to use the proceeds from this financing to support the continued development of our pipeline.
And to potentially drive its expansion through the in licensing of an additional complementary product candidate.
With that I'll now.
Now hand, the call over to Dr. <unk> to provide you with more detail on our critical programs and development strategy.
Mark.
So thank you Steve and thanks, once again to all of you who have joined us today.
I'll begin today with an update on the status of our lead neurosis cyclic program at.
As some of you may know <unk>, the cyclic formerly known as O N 123 300.
Simultaneously inhibits both the cell cycle and cellular metabolism through CDK and arc five respectively.
This differentiates <unk> from currently approved CDK, four six inhibitors and positions it.
Potential treatment for patients that are refractory or have become resistant to.
Through these agents.
This may be significant as CDK four six inhibitors generate more than $6 billion in worldwide sales in 2019 alone.
In vitro <unk>.
The router cycle.
Was shown to inhibit the growth of the number of cancer cell lines, including breast cancer that are resistant to powerboat side club, which is the most widely prescribed CDK four six inhibitor.
No RASM sideslip also inhibit CDK four more potently than powerball cyclic and exhibited improved on target toxicity in in vivo preclinical studies as evidenced by a decrease in neutropenia.
We believe that normal cycle potent kinase inhibition profile and potentially improved safety profile may ultimately provide strong anti cancer activity and facilitate continuous daily dosing in patients.
This would provide another important point of differentiation for <unk>.
<unk>, nor as the cyclical and the currently approved CDK four six inhibitors, such as powerful cyclic and driver side.
These agents are prescribed in combination with an anti estrogen.
In the three week on.
One quick off treatment schedule due to issues of tolerability, including side effects related to neutropenia or low white blood cell counts.
Our hope is that <unk> safety and efficacy profile will initially position.
As a novel treatment option for CDK, four six inhibitor refractory patients.
I'll also providing it with an opportunity to move first line therapy in the future.
We are evaluating it continuous oral daily dosing schedule and our ongoing phase one study in the U.
This multi center trial six to enroll patients with advanced cancers, including but not limited to hormone receptor positive her two negative metastatic breast cancer, who are refractory to or progressing on currently approved CDK four six.
<unk>.
To date, we have completed enrollment in the first cohort.
With 40 milligrams orally once a day <unk>.
Our currently enrolling patients in the second cohort at 80 milligrams orally once a day.
In parallel with our U S. Phase one study we are also advancing a phase one study in China in collaboration with our partner <unk> biopharmaceutical.
This trial is designed to complement our U S study by evaluating a three week on one week off dosing schedule of oral neurosis cycle today.
To date, the hammocks trial is fully enrolled the third dose cohort at 120 milligrams orally once a day.
Study is currently enrolling the fourth dose cohort at 160 milligrams orally once a day.
No cases of grade three or higher neutropenia or other dose limiting toxicities have been seen to date in either trial.
Together, we expect findings from the complementary trials in the U S and China.
To inform the recommended phase II dose and treatment regimen for future trials, including a phase II basket study that will enroll patients with several different types of cancer.
Based on preclinical models, one type of cancer, we intend to enroll includes the hormone receptor positive her two negative metastatic breast cancer patients who are resistant to the approved second generation CDK <unk> inhibitors, we expect to initial.
Kate This trial in the second half of next year.
Beyond our planned basket study, we also expect the findings.
Our ongoing phase one program to inform the design of one or more additional clinical trials that will evaluate the safety and efficacy of Nebraska cyclic in combination with other anti cancer agents.
Specific plans around these trials are currently under development.
And we'll be shared once they have been finalized.
Moving on I would now like to discuss our investigator initiated programs evaluating <unk> or Ras pathway modulator, which continues to make exciting progress.
Our last earnings call.
We discussed recently published preclinical data that demonstrated the ability of <unk> to synergize with checkpoint inhibitors by reversing the immunosuppressive tumor microenvironment through the Upregulation of novel antigens, such as <unk> 40 <unk>.
Yourself.
In September we then reported very encouraging preliminary clinical data, suggesting that the observed preclinical synergy between Greek assertive in checkpoint inhibition may translate to patients and potentially provide meaningful clinical benefit.
These data were from the phase one two way investigator initiated trial evaluating <unk> in combination with the PD, one checkpoint inhibitor <unk> in patients with advanced K Ras mutated non small cell lung cancer.
I'll provide a short recap of this encouraging data now.
Which is topical given that November is lung cancer awareness month.
Results from the trials preliminary readout.
Note that two out of seven Evaluable patients achieved a resist defined partial response with another patient showing stable disease, which gives objective response and disease control rates of 29% and 43% respectively.
In addition, the study doublet of <unk>, and <unk> was well tolerated and the maximum tolerated dose of the doublet was not reached.
Taking a closer look at the study design and data there are several key points that have generated a high level of enthusiasm from key opinion leaders and would speak to just power encouraging initial.
Initial findings are.
The first point is related to the patient population enrolled in the study.
These patients were extensively pretreated with nine of 12, having failed at least two prior lines of therapy and all enrolled patients failed at least one line of prior therapy with a PD one checkpoint inhibitor.
This is significant as PD one is the target of Navona map, which was administered in combination with <unk> the.
The fact that we were able to achieve responses in patients who previously failed.
Therapy targeting the PD, one checkpoint by combining an anti PD one therapy with <unk> provides encouraging evidence of <unk> ability to synergistically combine with checkpoint inhibitors and augment their efficacy and K Ras mutated cancers.
This is important as K Ras mutations are predominant genetic driver of non small cell lung cancer and there is currently a lack of effective treatment options for these patients who failed to adequately respond to checkpoint inhibitor therapy.
A second keep finding from the preliminary data readout that I would like to highlight is related to the underlying Barry K Ras mutations of patients achieving a partial response or stable disease, each of which was different.
This speaks to Rico circuit mechanisms of action, which is not specific to a particular K Ras variance.
As Qi <unk> see.
This provides an important point of differentiation between <unk> and other Ras pathway modulators targeting particular, K Ras variants, such as G 12, C and potentially positions <unk> to be more broadly applicable.
Lastly, I should note that you observed radiographic responses were seen in both the lung or the primary tumor site and at multiple metastatic sites, which are the major cause of death for these patients.
Collectively the preliminary data from this phase <unk> study together with the preclinical data we discussed on our last earnings call suggests that Rico started may synergize with checkpoint inhibition and that Rico, Sir to checkpoint inhibitors.
Combinations may be applicable not only to K Ras mutated non small cell lung cancer, but two other indications.
Where PD, one or PDL, one inhibitors are the standard of care such as melanoma.
Looking ahead, the phase <unk> non small cell lung cancer trial continues to enroll patients as part of the expansion phase at the highest dose of oral rig assertive as defined in the protocol.
We and the principal investigators intend to complete the trial per protocol and anticipate opening additional excuse me anticipate reporting additional data from this study in 2022.
In parallel and additional studies that will allow for further dose escalation is also under consideration.
Since the maximum tolerated dose of the <unk> doublet was not reached in the ongoing trials dose escalation phase which has been completed.
Based on the data from these two trials, we hope to identify the doublet to recommended phase two dose and better inform its clinical development.
Beyond the investigator initiated K Ras mutated non small cell lung cancer trial, we intend to further leverage the immuno therapeutic effects of <unk> through a separate investigator initiated study evaluating <unk> in combination with.
It's a PD one checkpoint inhibitor in advanced recurrent malignant melanoma.
This trial is supported by both the encouraging preliminary data from the non small cell lung cancer trial and by the preclinical melanoma studies that were featured in the peer reviewed publication out of Andrew belts that we discussed on our last call.
We and the investigators are currently finalizing the protocol for this trial it will be submitted to the FDA and expect that it will be initiated in the first half of 2022.
Moving on I'd like to speak very briefly about the investigator initiated trial evaluating <unk> monotherapy in advanced squamous cell carcinoma associated with recessive dystrophic Epidermolysis <unk> below <unk>.
Our R&D E D.
As Steve mentioned this is an ultra rare condition with an extremely high unmet medical need as it is invariably payroll.
It's caused by a loss of expression of key protein collagen, seven which causes extreme skin fragility and chronic wounds formation.
Over time <unk>.
Many patients develop squamous cell carcinoma with the over expression of polo like kinase, one or <unk> one.
The scientific rationale for the ongoing trial of <unk> in this indication.
Was suggested by a leading expert on our D. E. B comes from that drug screens that identified <unk> as the most potent inhibitor of polo like kinase, one or P. L. K one test.
We've seen promising evidence of <unk> clinical activity in this indication to date and plan to provide additional updates on the trials data as it matures as well as at a medical meeting.
In the upcoming months.
Finally, before handing off the call.
To Mark Guerin to talk about our financials I'd like to reemphasize one point.
While we are of course very interested in the outcomes of the ongoing investigator initiated studies and plan to continue evaluating opportunities to potentially initiate additional studies of this nature, we remain committed to preserving our primary focus and resources on neurosis cycle.
We believe this strategy is the best way to ensure the efficient advancement of our lead program, while positioning us to generate value to recur Sir to continue development and high unmet need indications.
And with that I'll turn the call over to Mark Guerin for a discussion of our Q3 financial results Mark.
Thanks, Mark and good net good afternoon, everyone I'll begin with a quick review of our third quarter expenses, and then I'll discuss our cash position and cash runway.
Research and development expenses for the third quarter of 2021 were $1 8 million and this compares with $4 2 million for the third quarter of 2020.
The decrease was primarily related to higher expenses related to the inspire study in the 2020 period.
General and administrative expenses for the third quarter of 2020 about $2 3 million and this compares with $2 1 million for the third quarter of 2020.
The increase was primarily related to expenses for Investor relations proxy solicitation and fees related to our AGM and special meeting by proxy in 2021.
We reported a net loss for the third quarter of 2021 of $3 5 million or <unk> 22 per share on 16 million weighted average shares outstanding.
This compares with a net loss in the third quarter of 2020 of $6 2 million or <unk> <unk> per share on $12 1 million weighted shares outstanding.
Cash and cash equivalents as of September 32021 were $59 4 million versus $19 million as of December 31, 2020.
Our average quarterly operating cash burn in 2021 has been a $4 3 billion.
We believe that our cash position will be sufficient to fund our ongoing clinical trials and business operations through the achievement of significant milestones, including pursuing corporate development opportunities and should be sufficient for more than two years.
This completes my financial review I'll now turn the call back to Steve.
I'd like to thank both marks for the thorough review.
Just heard.
In summary.
We have multiple key near term milestones and value drivers ahead of us.
And our lead <unk> program.
We expect our phase one studies in the United States and China to continue progressing and anticipate selecting a recommended phase two dose in the first half of next year.
This would then be followed by the initiation.
All of our phase II basket trial.
The gallon to described including indications such as hormone receptor positive <unk>.
<unk> negative metastatic breast cancer in the second half.
1022.
In Riga assertive investigator initiated program.
That to report additional data from the ongoing.
K Ras mutated non small cell lung cancer trial in 2022.
We also expect an additional investigator initiated studies evaluating Vega assertive.
Combination with a PD one inhibitor in advanced melanoma patients to begin in the first half of the next year.
Finally, we continue to actively evaluate strategic licensing opportunities.
To enhance our product portfolio.
As with all of our decisions.
Any decision on this front will be driven by excellent science and the potential for clinical benefit.
An indication.
Unmet medical need.
So with that review of our clinical progress and our financial results.
Like to open the call for questions.
Operator.
Thank you and ladies and gentlemen, if you wish to register for a question for todays question and answer session. You will need to press Star then the number one on your telephone.
Question has been answered and you wish to withdraw your request you may do so by pressing the pound key.
If you are using a speakerphone. Please pick up your handset before entering your request one moment. Please for the first question.
And our first question is from Dr. Charles <unk> of Guggenheim Securities. Your line is open.
Yes.
Good evening, guys and thanks for taking my question.
I had one on the resi cycle as you look towards potentially identifying a recommended phase two dose in the first half of next year.
When are you guys thinking about disclosing these data and given you're potentially differentiated mechanism of action how would you set expectations about that data. Thanks.
Thanks, Charles and I'll ask Dr. <unk> to take that question Mark.
Yes.
Yes, so I think that the.
Data will be disclosed initially at a medical meeting.
Of some sort of followed by publication, but.
The data will be disclosed to the medical meeting and.
In terms of the second question I think that.
We have.
We are currently considering.
Several different buckets or baskets for the basket trial I tumor types to evaluate.
And we're continuing to refine that list over time based on the RNA supervision profile.
That we have with <unk>.
And we'll also be influenced to some degree by hints of activity or different signals that we see during the course of the phase one study.
<unk>.
And then we will as that information.
It gets further distilled.
And it becomes a <unk>.
More set in stone so to speak then we will make that public but Steve I don't know if you want to comment further.
No I think a usual markers comprehensive of course, we're looking for signals in the phase of an efficacy trial.
And once we create the Buck and trial, which will probably be mono neuralgia cyclic, but we also will be looking at the potential for combinations of neurons of cyclin E. B that was an anti estrogen that with immuno oncology drugs will be considering those.
Coaches as well.
Yeah.
Understood. Thanks for taking my questions.
Thank you Charles.
Thank you.
Next question is from Joe <unk> of H C. Wainwright Your line is open.
Good evening, everyone. This is Matt on for Joe. Thanks for taking our question. So just quickly we were wondering if and maybe we're kind of in licensing you guys might be looking at and if any of that could be complementary to some of the current assets you guys are making some pretty great progress in the pipeline.
Oh pardon me would you like to answer Matt's question. Please sure sure. Thanks for the question, Matt and were quite excited about our existing programs and the rise of cyclone and Northcote started after Gallagher and doctor freshman between them, but they've been a part of over a dozen oncology drug approvals and excited about our existing pros.
Graham So when we look at that adding a complementary program as Dr. <unk> stated in his remarks, we're looking at what fits best in the portfolio is another shot on goal or towards further.
Further expanding our pipeline and look forward to updating our progress on that in the future.
Yeah, great. Thanks, Thanks for taking my question.
Thank you and our next question is from Dr. Robert.
<unk> of Nobel Capital Your line is open.
Good evening.
Thank you for the great comprehensive summary of the products.
Dr Guilders summary of.
Now recycling.
There were some points about the comparison with with palmar cycling.
Could you just clarify the differentiating factors in the different targets that you would discuss just briefly.
I'll ask <unk> to take that and also that to Cosenza. After Mark's comments may want to add to that.
Okay.
Compared to the CDK four agents.
Agents.
Yes, so if we if we look at.
Neurosis cyclic and we then look at Cabos cycle, and we looked at the in the CRO.
<unk> kinase inhibition profile.
In terms of the inhibition of CDK, four or one to three or <unk>.
I actually have a little more potent than is alba.
If we look at CDK six.
Neurosis cyclic is less potent than is powerful and this may be.
He's the.
Maybe.
Underlying <unk>.
Cause or may be responsible for the decrease in neutropenia that we have seen.
Clinically.
In the mouse model when we compare in RASM cyclic.
Oh and 123.
And our book.
We'll have to see how this plays out.
In.
The phase one study the dose escalation study, we will have to look carefully at the AE profile our safety profile.
Right.
There are.
Several other kinases.
That.
Oh, and 123 or more astrocytes glib hits.
That either a powerboat side clip dosing.
At all or it hits much more weekly or less potently based on the in vitro kinase.
Profiles, but.
And these include things like our five.
With three.
Yeah.
<unk>.
Please see the GFR.
Et cetera et cetera. So there are when you look at them side by side there are several kinases that.
We have activity against Pablo just does not.
So I'm not sure. If this is answered your question or not if not.
Happy to try and expand a little bit further or Steve may want to expand further as well.
Well actually perhaps Steve kazanjian, we'd like to.
Add something based on our preclinical studies to date, Steve do you have anything to add.
Tomorrow.
Comments sure. Thank you that's a great question.
Robert.
The differentiating point based on in vitro data as Mark and Patrick Gallagher had spoke to previously.
That helps.
Although the CK forces inhibitors were either sick leave is the most specific.
And Paolo cyclic is following the most specific and then you have Adam Mystic lid, and narrow circle, which are both.
Because they're multi kinase inhibitor and.
On side by side testing there are differences among those two especially about apparel cyclically.
And what we believe is differentiating points can be found in those targets both for efficacy and for toxicity profiles.
In published data that we have you can see that cell lines.
Treat it with tableau cyclic versus once you're through <unk>.
We induce April to assist we inhibit the AK T.
And EMCORE pathways, which are important for tumor survival and these are not done it publicly so we induce a more subtle toxic sooner type of treating tumor cells, whereas <unk>.
And rigor.
And abbvie induce more of a sort of static Adam cyclically, but also and this is sort of.
Constant affecting certain teamster lines.
<unk> like 123, or <unk> and again, we believe these are based on <unk>.
Targets, however, amongst the four CDK four and six inhibitors, we are the only one that induces inhibits.
It's not unusual inhibits arc five and arc five is a very interesting target under our nose.
No no.
<unk>.
Inhibitors for arc five however, this is a very important.
Target for tumor cell survival, not so much to proliferation of tumor cells for.
The survival of tumor cells and a hypoxic conditions. So we believe this is.
It will be very beneficial.
As part of our mechanism of action.
Okay great.
Yeah.
You actually did answer the question I was really interested in how <unk> compares in terms of the targets.
The potency and the breadth of targets with the approved drug so thank you very much.
Youre welcome. Thank you.
Thank you Michelle.
I'm showing no further questions in the queue at this time I'd like to turn the call back to the speakers for any closing remarks.
Thank you Laurie and to all our participants today.
Thank you for participating in today's update call.
We look forward to executing on our business plan and to keep you appraised of all of our progress.
We appreciate your continued interest in our programs and your insightful questions.
Again and have a lovely evening I would hope to interact with all of you again soon.
Take care.
And ladies and gentleman. Thank you for your participation on today's conference call.
Concludes today's event and you may now disconnect.