Infinity Pharmaceuticals Inc

OTC:INFIQ

Earnings Call Transcript 2022-Q3

[Operator]

Ladies and gentlemen, thank you for standing by. Welcome to the Infinity Pharmaceuticals Conference Call to discuss the Company's Third Quarter 2022 Financial Results and Business Update. My name is Michelle, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at Infinity's request.

Now I would like to introduce your host for today's call, Jayne Kauffman. Please go ahead.

[Jayne Kauffman, Senior Executive Coordinator]

Thank you, Michelle, and good morning, everyone. Welcome to today's call to discuss our third quarter 2022 financial results and the MARIO-3 data update that we announced in a separate press release earlier this morning. Both press releases are available on our Web site at infi.com.

On the call with me today are Adelene Perkins, Chief Executive Officer and Chair; Larry Bloch, President; and Robert Ilaria, Jr., Chief Medical Officer. We'll open up the call for Q&A following our remarks.

Please note that during this call, we may make forward-looking statements about our future expectations and plans, including clinical development objectives, the therapeutic potential of our product candidates, our strategic plans, and financial projections. Our actual results may differ materially from what we project today due to a number of important factors, including the considerations described in the risk factor section of our annual report on Form 10-K for 2021. And then, other filings we make with the SEC. These forward-looking statements represent our views only as of today. And we caution you that we may not update them in the future whether as a result of new information, future events, or otherwise.

Now, I'd like to turn the call over to Adelene.

[Adelene Perkins, Chairman and Chief Executive Officer]

Thanks, Jayne, and thank you to everyone for joining us to review Infinity's third quarter 2022 business update. Today, we are pleased to provide encouraging updated data from our single-arm MARIO-3 Phase 2 trial evaluating eganelisib in combination with atezolizumab and nab-paclitaxel in patients with front-line metastatic triple negative breast cancer or TNBC. We are encouraged by the updated results, which continue to show durable long-term clinical benefit for patients, which we will review shortly.

As we disclosed on our second quarter earnings call, we have made entering into a strategic partnership to advance eganelisib's development and pave the way to eventual approval are top priority. We plan to initiate additional studies of eganelisib after putting a partnership in place to ensure that we and our partner are aligned on eganelisib's future development.

Let me bring you up to date on our progress. Our business development discussions are directed towards an initial focused development plan in a randomized-controlled setting. The benefit seen across a broad array of solid tumors in which eganelisib has been studied to-date, including breast, urothelial, head and neck, ovarian, and melanoma cancers provide multiple potential future development tests. It is our goal to announce the partnership and the focus of the prioritized clinical development plan for eganelisib in the third quarter of 2023.

Turning to the MARIO-3 data, with an additional year of data maturity since our last update at the San Antonio Breast Cancer Symposium in December 2021, there is encouraging evidence of a long-term benefit for patients relative to the IMpassion130 benchmark study. We are now able to report one-year progression-free survival rates for patient with both PD-L1 positive and PD-L1 negative tumors, which were promising for all patients regardless of PD-L1 status. This long-term benefit in patients with TNBC is consentient with the long-term benefit seen in other indications, in which, eganelisib has been studied. Additionally, there were no new safety signals during the extended period of treatment.

We are also pleased to report positive updated results from the randomized-controlled MARIO-275 Phase 2 clinical study evaluating eganelisib plus nivolumab versus nivolumab in patients with second-line platinum-resistant metastatic urothelial cancer during the third quarter. As we previously reported, the eganelisib combination showed approximately a doubling of patient's overall survival as the two-year landmark analysis compared to standard of care nivolumab monotherapy.

Eganelisib has demonstrated promising clinical results across five oncology indications and treatment settings to date. The continued strength of our data across multiple indications provide solid evidence that eganelisib has the potential to be a transformative therapy in immuno-oncology for three key reasons. First, we have a first-in-class therapy with potent and specific on target activity and translational data showing that target inhibition with eganelisib reprogrammed macrophages in the tumor-like environment, reduces immune suppression, and activates an anti-cancer immune response. Second, the clinical data with eganelisib have demonstrated prolonged progression-free survival in multiple indications and extended overall survival over current standards of care in a randomized-controlled trial that allowed us see the distinct contribution of eganelisib over its combination drug partners. Third and very importantly, eganelisib has been shown to have an acceptable and manageable safety profile in combination with other drug including in two- and three-drug combination regimens.

At this time, I would now like to just turn the call over to Dr. Ilaria to review our recent encouraging eganelisib data. Rob?

[Robert Ilaria, Chief Medical Officer]

Thank you, Adelene. Good morning. The objective of our MARIO-3 TNBC Phase 2 study was to evaluate the safety and efficacy of the addition of eganelisib to atezolizumab and nab-paclitaxel in front-line metastatic TNBC patients. Patients were enrolled in either PD-L1 positive or PD-L1 negative tumor cohorts. The eligibility criteria for MARIO-3 were designed to the mirror the IMpassion130 study to facilitate benchmarking.

It's important note that the approval of immune checkpoint inhibitors in combination with chemotherapy in front-line metastatic TNBC have been limited to PD-L1 positive tumors. There are no immune checkpoint inhibitor regimens approved for patients with metastatic PD-L1 negative tumors which represent approximately two-thirds of TNBC patients. As of October 8, 2022, 62 TNBC patients were enrolled in a valuable for safety and 57 patients were valuable for efficacy in MARIO-3 with a median duration of follow-up of 10 months.

In the efficacy dataset, 35 patients had PD-L1 negative tumors, 18 patients had PD-L1 positive tumors, and 8 patients had tumors of undetermined PD-L1 status. We are pleased to share that we continue see very encouraging and durable evidence of a progression-free survival benefit in this study. In patients with PD-L1 negative tumors, we continue to see an improvement in median PFS with a median PFS of 7.3 months in MARIO-3 compared to 5.6 months in IMpassion130 as 30% relative improvement.

Even more importantly, we are also seeing evidence of potential long-term benefit with a one-year PFS rate of 34.7%. Although the one-year PFS rate was not disclosed for the IMpassion130 PD-L1 negative population, it should be noted that the one-year PFS rate in MARIO-3 PD-L1 negative tumors, a subgroup with inferior outcomes with immune checkpoint inhibitor therapy, exceeds the 23.7 one-year PFS rate for the IMpassion130 ITT, which of course included patients with PD-L1 positive and negative tumors.

In patients with PD-L1 positive tumors, we also observed evidence of potential long-term benefit with a one-year PFS rate of 37.5% compared to 29.1% in IMpassion130, a 29% relative improvement. In addition to the encouraging one-year PFS rate, we observed further evidence of anti-tumor activity of the eganelisib triplet in patients with PD-L1 positive tumors. The objective response rate was 66.7% compared to 58.9% in IMpassion130 is largely driven by a higher complete response rate in MARIO-3 patients with the PD-L1 positive tumors, 16.7% versus 10.3% of patients in IMpassion130.

Lastly, the median duration response was 11.7 months compared to 8.5 months in IMpassion130, a 38% relative improvement. We did not continue to see improvement in a median PFS of the MARIO-3 PD-L1 positive population with a median PFS of 6.4 months compared to 7.5 months on IMpassion130. With the approval of pembrolizumab plus chemotherapy in patients with PD-L1 positive tumors, this proved to be a challenging patient population to enroll, which provided us with a less robust sample size to characterize the median PFS compared to our PD-L1 negative patient cohort.

Nonetheless, the one-year PFS rate, an indicator of potential long-term benefit, was very consistent across PD-L1 tumor status in MARIO-3, 37.5% in PD-L1 positive tumors and 34.7% in PD-L1 negative tumors. These combined for a one-year PFS rate of 36% in a MARIO-3 ITT, a 52% relative improvement over the one-year PFS rate of 23.7 reported in the entire IMpassion130 population. The updated safety analysis in the MARIO-3 TNBC triplet regimen remains consistent with expectations for the three component drugs. And no new safety signals were observed during the extended time on treatment. The most common Grade 3 or higher treatment-related adverse events were hepatic AEs at 24.2%; neutropenia AEs at 14.5%, and skin and peripheral neuropathy adverse events, each had 11.3%.

25.8% of patients discontinued treatment for treatment-related AEs, which for a triplet regimen compares favorably to the 19.1% reported in IMpassion130 for the atezolizumab and nab-paclitaxel doublet. While hepatic AEs remain the most common Grade 3 or higher treatment-related adverse events when eganelisib is combined with an immune checkpoint inhibitor, they continue to be reversible within a relatively short amount of time, often without corticosteroids. Bilirubin elevation was infrequent, and we saw no evidence of Hy's Law.

In summary, the almost one-year greater data maturity in MARIO-3 TNBC has provided us a new opportunity to gain insight into potential long-term benefit of the triplet regimen of eganelisib combined with atezolizumab and nab-paclitaxel with encouraging one-year progress-free survival rates across tumor PD-L1 status. These findings build on the promising two-year landmark overall survival data Adelene described from our MARIO-275 randomized trial in second-line platinum-resistant urothelial cancer. Data from our Phase 2 studies are consistent with and build upon findings in our MARIO-1 Phase 1b study where we demonstrated potential for eganelisib to benefit patients' refractory to immune checkpoint inhibitors, such as patients with squamous cell cancer of the head and neck. The totality of the eganelisib data across multiple tumor types are important next steps in a robust, randomized clinical trial setting.

Now, I'll turn the call over to Larry to review our third quarter financial results. Larry?

[Larry Bloch, President]

Thank you, Rob. During the third quarter, we continued to pursue a disciplined, prudent approach to capital allocation. So, at the end of the third quarter of 2022, Infinity had total cash of $47.2 million compared to $80.7 million at December 31, 2021. Research and development expenses for third quarter of 2022 were $7.7 million, compared to $7.1 million at the same period in 2021. And this increase is primarily related to higher compensation expense due to additional staff for the future development of eganelisib. General and administrative expense was $3.5 million for the third quarter of 2022 as compared to $3.8 million the same period in 2021.

And the increase was primarily due to a decrease in special services. Net loss for third quarter of 2022 was $10.7 million or a basic and diluted loss per common share of $0.12, compared to net loss of $10.7 million or basic and diluted loss per common share of $0.12 in the same period in 2021. Infinity's financial guidance for 2022 remains unchanged. We continue to expect net loss for 2022 to range from between $40 million and $50 million, and 2022 year-end cash to range from between $35 million and $45 million. Infinity's finance guidance does not include additional financing or business development activities even as our goal was to execute on eganelisib strategic partnership to be announced in the first quarter of 2023.

At this time, we can open up the call for questions.

[Operator]

Thank you. [Operator Instructions] And our first question comes from the line of Edward Tenthoff with Piper Sandler. Your line is open, please go ahead.

[Edward Tenthoff, Piper Sandler]

Great. Thank you very much, and thanks for the update on the MARIO data today. Should we be expecting a presentation at San Antonio Breast, will you be presenting there or is this sort of the update for this year? And appreciate that and all the other comments too. Thanks.

[Adelene Perkins, Chairman and Chief Executive Officer]

Thank you, Ed, for the question. This is the data update for MARIO-3. As you know, we have presented as San Antonio Breast Cancer Symposium for the last two years, and so we chose this year to present the data on this call so that we could have the most recent data cut to get the data out more quickly. As you know, there's a longer lead time toward the medical meeting.

[Edward Tenthoff, Piper Sandler]

Yes, makes a lot of sense. I appreciate it. And congrats on the data, it looks great.

[Adelene Perkins, Chairman and Chief Executive Officer]

Thank you.

[Operator]

Thank you. [Operator Instructions] And our next question comes from the line of Soumit Roy with Jones Research. Your line is open, please go ahead.

[Soumit Roy, Jones Research]

Hi, everyone. Thank you for the update. Just trying to understand the new 13 patients versus the pervious update, is anything particular about these patients that pulled back the median PFS number or did the PD-L1 expression levels go up more than expected? Any color would be appreciated.

[Adelene Perkins, Chairman and Chief Executive Officer]

Thanks, Soumit. The most important update in this data is that it's more mature, and so that was what we were really focused on and are pleased to see the one-year PFS rate, which we think is a most meaningful reflection of long-term benefit. But perhaps, Rob, you can elaborate a little bit further on the median PFS?

[Robert Ilaria, Chief Medical Officer]

Sure. Last year, when we provided the data, we were updating date from almost a year ago. And one of the challenges in the median PFS, of course, is that the middle value of whatever list of number of patients you have. And one of the challenging things that we had is that the PD-L1 positive patient population proved a bit more challenging to enroll. Once [pembro chemo] [Ph] got approved, I think a lot of those patients were seen in the community and not in a lot of the research centers. So, as a result, we weren't able to get as many patients in the PD-L1 positive group as negative. And as a result, that midpoint can really fluctuate a lot. And so, last year, there were some patients who hadn't had even their first scan yet. So, I think the challenges of median PFS can really be variable when you have a smaller sample set compared to, for example, our PD-L1 negative set was almost twice what the positives were.

[Soumit Roy, Jones Research]

That's it. Thank you so much.

[Operator]

Thank you. [Operator Instructions] And our last question comes from the line of Kalpit Patel with B. Riley. Your line is open, please go ahead.

[Mayank Mamtani, B. Riley]

Good morning, team. Thanks for taking our questions and congrats on the project. This is Mayank on for Kalpit. So, maybe focusing on your partnership discussions that are ongoing for UC versus TNBC, has there been any interest relatively higher in one indication versus the other, and maybe which do you anticipate being the first to advance to the next stage? And then I have a quick follow-up.

[Adelene Perkins, Chairman and Chief Executive Officer]

Okay, thank you for the question. Well, we're not in a position today to describe the specifics on the future of eganelisib's development plan until we've put the partnership in place. We can tell you a few things that you might expect to see in a future development. First is that it will be leveraging some of the encouraging data that we generated with eganelisib today in one more indication. The focus of the development will be in a randomized-controlled setting so that we can very clearly show the contribution of eganelisib over its contribution regimen over a standard of care. And three, it will be in a patient setting where there's a high unmet need. So, we've seen the benefit of eganelisib across a broad array of solid tumors. It gives us many potential development paths, as you mentioned, breast, urothelial, head and neck, ovarian melanoma. And so, we're going to -- we're prioritizing that with a prospective partner, and we look forward to announcing the details of the partnership and the first next trial and potential subsequent next trials in the first quarter of 2023.

[Mayank Mamtani, B. Riley]

Thank you for that color. And just a kind of related follow-up, and in these discussions then, and your own with KOLs, and also coming away from the [SABC] [Ph] Conference over the weekend, any thoughts on what registration study could look like in the context of PD-L1 status, positive or negative, and if there is an opportunity to lump them together also as a kind of a novel trial design. Could you comment on that, would be helpful?

[Adelene Perkins, Chairman and Chief Executive Officer]

Sure. I'll turn it over Rob, and just highlight that we have seen benefit with eganelisib in patients across multiple different tumor types regardless of PD-L1 status. Of course, a registrational trial will depend on what is the approved standard of care in those different patient populations. And maybe, Rob, you can elaborate further?

[Robert Ilaria, Chief Medical Officer]

Sure. And also, I mean regarding the TNBC question specifically, it's true we are seeing pretty consistent one-year PFS rates across PD-L1 negative and positive tumors, which certainly is very encouraging. They're -- certainly in thinking about path for our TNBC, one could be going for both patient populations, although now that there's a different standard of care for those two populations, it does make it a complex and probably large trial because of the two different control arms. The PD-L1 negative is certainly a great story, the lead checkpoint inhibitors haven't been successful there. So, certainly, you could argue that the greatest unmet need is in that PD-L1 negative group. So, that's certainly also a very attractive path. And as Adelene mentioned, we believe the TNBC data kind of adds to the totality of the data. So, I think which way you decide to go, which tumor, which indication within a tumor, I think will be very much influenced by who our partner is, and their preferences as well.

[Mayank Mamtani, B. Riley]

Thanks for taking our question, team, and look forward to additional updates.

[Operator]

Thank you. And I'm showing no further questions at this time. And I'd like to turn the conference back over to Adelene for any further remarks.

[Adelene Perkins, Chairman and Chief Executive Officer]

Thank you, Michelle, and thank you all for joining us today. We are really enthusiastic about the data that we have generated, and the progress of advancing eganelisib for the potential treatment of patients with cancers who are in dire need of improved therapy. So, we look forward to updating you on our business development efforts and the focus of the next study for eganelisib in the coming months. Thank you for your continued support.

[Operator]

Thank you. This does conclude today's conference. You may all disconnect. Everyone, have a great day.