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spk06: The conference will begin shortly. To raise your hand during Q&A, you can dial star 1 1. The conference will begin shortly. To raise your hand during Q&A, you can dial star 1 1.
spk11: 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 will 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 this call is being recorded at Infinity's request. Now I would like to introduce your host for today's call, Jane Kaufman. Please go ahead.
spk10: 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 website at infi.com. On the call with me today are Adeline Perkins, Chief Executive Officer and Chair, Larry Block, President, and Robert Elaria, Jr., Chief Medical Officer. We will 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 consideration considerations described in the risk factors section of our annual report on Form 10-K for 2021 and in 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 Adeline.
spk09: Thanks, Jane. And thank you to everyone for joining us to review INFINITI's third quarter 2022 business update. Today, we're pleased to provide encouraging updated data from our single-arm MARIO3 phase two trial, evaluating agamelisib in combination with atezolizumab and nabpaclitaxel in patients with frontline 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 Eganilisib development and pave the way to eventual approval our top priority. We plan to initiate additional studies of Eganilisib after putting a partnership in place to ensure that we and our partner are aligned on aganalysib'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 benefits seen across a broad array of solid tumors in which aganalysib has been studied to date, including breast, urothelial, head and neck, ovarian, and melanoma cancers provide multiple potential future development tabs. It is our goal to announce a partnership and the focus of the Prioritized Clinical Development Plan for Ganalysib in the third quarter of 2023. Turning to the Mario3 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 IMPASSION 130 benchmark study. We are now able to report the one-year progression-free survival rates for patients 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 consistent with the long-term benefits seen in other indications in which agamalizib has been studied. Additionally, there were no new safety signals during the extended period of treatment. We were also pleased to report positive updated results from the randomized controlled MERIO275 Phase II clinical study evaluating agamalizib plus nivolumab versus nivolumab in patients with second-line platinum-resistant metastatic urothelial cancer during the third quarter. As we previously reported, the agamelisib combination showed approximately a doubling of patient overall survival at the two-year landmark analysis compared to standard-of-care nivolumab monotherapy. Agamelisib has demonstrated promising clinical results across five oncology indications and treatment settings to date. The continued strength of our data across multiple indications provides solid evidence that aganalysib 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 targeted inhibition with aganalysib reprograms macrophages in the tumor microenvironment, reduces immune suppression, and activates an anti-cancer immune response. Second, the clinical data with aganalysib have demonstrated prolonged progression-free survival in multiple indications and extended overall survival over current standards of care a randomized controlled trial that allowed us to see the distinct contribution of aganalysib over its combination drug partners. Third, and very importantly, aganalysib has been shown to have an acceptable and manageable safety profile in combination with other drugs, including in two and three drug combination regimens. At this time, I'd now like to return the call over to Dr. Laria to review our recent encouraging aganalysib data. Rob?
spk01: Thank you, Adeline. Good morning. The objective of our MARIO3 TMBC Phase II study was to evaluate the safety and efficacy of the addition of aganalysib to atezolizumab and nabpaclitaxel in frontline metastatic TMBC patients. Patients were enrolled in either PD-L1 positive or PD-L1 negative tumor cohorts. The eligibility criteria for MARIO3 were designed to mirror the IMPASSION 130 study to facilitate benchmarking. It's important to note that the approval of immune checkpoint inhibitors in combination with chemotherapy in frontline metastatic TMBC 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 TMBC patients. As of October 8, 2022, 62 TMBC patients were enrolled in Evaluable for Safety, and 57 patients were Evaluable for Efficacy in MARIO3, with a median duration of follow-up of 10 months. In the efficacy data set, 35 patients had PD-L1 negative tumors, 18 patients had PD-L1 positive tumors, and eight patients had tumors of undetermined PD-L1 status. We're pleased to share that we continue to 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 MARIO3 compared to 5.6 months in IMPASSION-130, a 30% relative improvement. Even more importantly, we're 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 impassioned 130 PD-L1 negative population, it should be noted that the one-year PFS rate in Mario3 PD-L1 negative tumors, a subgroup with inferior outcomes with immune checkpoint inhibitor therapy, exceeds the 23.7 one-year PFS rate for the IMPASSION 130 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 IMPASSION 130, a 29% relative improvement. In addition to the encouraging one-year PFS rate, We observed further evidence of antitumor activity of the aganalysib triplet in patients with PD-1 positive tumors. The objective response rate was 66.7% compared to 58.9% in impassioned 130, largely driven by a higher complete response rate in MARIO3 patients with PD-1 positive tumors, 16.7% versus 10.3% of patients in impassioned 130. Lastly, the median duration of response was 11.7 months compared to 8.5 months in impassioned 130, a 38% relative improvement. We did not continue to see improvement in the median PFS of the MARIO3 PD-L1 positive population with a median PFS of 6.4 months compared to 7.5 months on impassioned 130. 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 MARIO3, 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 the Mario 3 ICT, a 52% relative improvement over the one-year PFS rate of 23.7 reported in the entire IMPASSION 130 population. The updated safety analysis of the Mario 3 TMBC 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 three 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 at 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 IMPASSION 130, for the atezolizumab and nabpaclitaxel doublet. While hepatic AEs remain the most common grade three or higher treatment-related adverse events, when aganalysib 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 Heye's Law. In summary, the almost one-year greater data maturity in MARIO3 TNBC has provided us a new opportunity to gain insight into potential long-term benefit of the triplet regimen of aganalysib combined with atezolizumab and apaclitaxel, with encouraging one-year progression-free survival rates across tumor PD-L1 status. These findings build on the promising two-year landmark overall survival data Adeline described from our MARIO275 randomized trial in second-line platinum-resistant neurofuel cancer. Data from our Phase II studies are consistent with and build upon findings in our MARIO1 Phase Ib study, where we demonstrate the potential for aganalysib to benefit patients refractory to immune checkpoint inhibitors, such as patients with squamous cell cancer of the head and neck. The totality of the aganalysib data across multiple tumor types supports 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?
spk03: 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 31st, 2021. Research and development expenses for third quarter 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 to support the future development of the Gantt-Olysses. 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. This increase was primarily due to a decrease in professional services. Net loss for the third quarter of 2022 was $10.7 million, or a basic and diluted loss per common share of 12 cents, compared to net loss of $10.7 million, or a basic and diluted loss per common share of 12 cents in the same period in 2021. And today'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. The business finance guidance does not include additional financing or business development activities, even as our goal is to execute on a Gantt-Listed strategic partnership to be announced in the first quarter of 2023. At this time, we can open up the call for questions.
spk11: Thank you. If you have a question at this time, please press star 1-1 on your touch-tone telephone.
spk00: One moment while we compile our Q&A roster.
spk11: And our first question comes from the line of Edward Tenhoff with Piper Sandler. Your line is open. Please go ahead.
spk02: 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 guidance too, thanks.
spk09: Thank you, Ted, for the question. We, this is the data update for Mario 3. As you know, we have presented at 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, get the data out more quickly. As you know, there's a longer lead time for the medical meeting.
spk02: Yes, makes a lot of sense. I appreciate it and congrats on that. It looks great.
spk09: Thank you.
spk11: Thank you.
spk00: One moment for our next question. And our next question comes from the line of Samit Roy with Jones Trading.
spk11: Your line is open. Please go ahead.
spk07: Hi, everyone. Thank you for the update. Just trying to understand the new 13 patients versus previous 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.
spk09: Thanks, Sumit. 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.
spk01: Sure. Last year, when we provided the data, we were updating data from almost a year ago. And one of the challenges in the median PFS, of course, is that's the middle value of whatever list of number of patients you have. And one of the challenging things that we had is that the P1 positive patient population proved a bit more challenging to enroll. You know, once PEMBRO chemo 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 P1 positive group as negative. And as a result, that midpoint can really fluctuate a lot. And so last year, you know, there were some patients who hadn't had even their first scan yet. So I think the challenge is that median PFS can really be variable when you have a, you know, a smaller sample set compared to, for example, our P1 negative set was almost twice what the positives were.
spk07: Thank you so much.
spk00: Thank you. One moment for our next question.
spk11: And our last question comes from the line of Patel with B. Riley. Your line is open. Please go ahead.
spk08: Good morning, team. Thanks for taking our questions and congrats on the progress. This is Mayank Khan for Calcutta. So maybe, you know, focusing on your partnership discussions that are ongoing for UC versus CNBC, has there been any interest, you know, relatively higher in one indication versus the other? And maybe, you know, which do you anticipate being the first to advance to the next stage? And then I have a quick follow-up.
spk09: Okay. Thank you for the question. While we're not in a position today to describe the specifics on the future of, again, ELISIB's development plan until we put the partnership in place, we can tell you a few things that you might expect to see in the future development. First is that it will be leveraging some of the encouraging data that we generated with again ELISIB to date in one or more indications. The focus of the development will be in a randomized controlled setting so that we can very clearly show the contribution of aganalysib 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 aganalysib across a broad array of solid tumors. It gives us many potential development paths, as you mentioned, breast, urothelial, head and neck, ovarian melanoma. 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.
spk08: Thank you for that, Kala. And just a kind of related follow-up, in these discussions and your own with KOLs and also coming away from the CITC conference over the weekend, Any thoughts on what a registration study could look like in the context of, you know, PD-L1 status, positive or negative? And, you know, if there's an opportunity to lump them together also as a kind of a novel trial design, could you comment on that? It would be helpful.
spk09: Sure. I'll turn it over to Rob and just highlight that we have seen benefit with, again, a list of patients across multiple different tumor types, regardless of PD-L1 status. 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.
spk01: Sure. And also, I mean, regarding the TMBC question specifically, you know, it's true we are seeing pretty consistent one-year PFS rates across beta-1 negative and positive tumors, which certainly is very encouraging. You know, certainly in thinking about pass for 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. Really, 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 Adeline mentioned, you know, we believe the TMBC data kind of adds to totality of the data. So I think, you know, 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, you know, their preferences as well.
spk08: Thanks for taking our questions, Dean. I look forward to additional updates.
spk11: Thank you, and I'm showing no further questions at this time, and I'd like to turn the conference back over to Adeline for any further remarks.
spk09: 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 GANalysa for the potential of 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 GANLISTS in the coming months. Thank you for your continued support.
spk11: Thank you. This does conclude today's conference.
spk00: You may all disconnect, everyone. Have a great day.
spk06: The conference will begin shortly. To raise your hand during Q&A, you can dial star 1 1.
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