On November 12, 2024 Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, reported financial results for the third quarter ended September 30, 2024, and provided a review of recent accomplishments and anticipated upcoming developments (Press release, Biohaven Pharmaceutical, NOV 12, 2024, View Source [SID1234648213]).

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Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "The team at Biohaven continues to advance multiple late and early stage assets that have the potential to change the current standard of care treatment paradigm across a number of diseases. Last quarter we announced positive topline results in our RWE trial assessing troriluzole for the treatment of spinocerebellar ataxia. Troriluzole (200 mg dosed orally) met the study’s primary endpoint on the change from baseline in the f-SARA at 3 years in all study population genotypes, showed statistically significant superiority after both 1 and 2 years of treatment, and achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. This was truly a watershed moment for the Company, given the implications of potentially bending the arc of one of the most intractable neurological diseases with no currently approved treatment options. SCA robs patients of their ability to speak, walk, and take care of themselves, and often shortens lifespans and has unfortunate intergenerational implications. We were encouraged by the robust dataset gathered to date and look forward to submitting an NDA to the FDA."

Dr. Coric continued, "We continue to execute across our broad pipeline including the recent initiation of our Phase 2 trial with BHV-2100 in acute migraine. Migraine burden and disability remain high despite advances in treatment; we believe our TRPM3 antagonistic approach has the potential to be a highly-effective, non-sedating, non-opioid treatment for pain and migraine. In the final months of 2024, we expect to report on a number of updates including SMA topline data and data across our MoDE platform including a SAD/MAD update and multiple INDs spanning β1AR for the potential treatment of dilated cardiomyopathy, galactose deficient IgA for IgA nephropathy and a further optimized IgG degrader for use in rare diseases."

Third Quarter 2024 and Recent Business Highlights

Achieved positive topline results in pivotal study of troriluzole in SCA – In September 2024, the Company announced positive topline results from pivotal Study BHV4157-206-RWE demonstrating the efficacy of troriluzole on the mean change from baseline in the f-SARA after 3 years of treatment. The study achieved the primary endpoint and showed statistically significant improvements on the f-SARA at years 1 and 2. Additionally, troriluzole achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. SCA patients treated with troriluzole showed a 50-70% slowing of disease progression, representing 1.5-2.2 years delay in disease progression over the 3-year study period. The Company intends to submit an NDA to the FDA for troriluzole in the treatment of all SCA genotypes in 4Q 2024. The development program for troriluzole has been granted orphan and fast track designations, and is eligible for priority review. European Medicines Agency marketing authorization remains under review and Biohaven completed a clarification meeting with CHMP Rapporteurs in 4Q 2024. MAA documents are being updated to include the new positive BHV4157-206-RWE study data with broader indication to include all SCA genotypes.

Initiated Phase 2 trial evaluating BHV-2100 in the acute treatment of migraine – In September 2024, the Company initiated a Phase 2 study of an orally administered TRPM3 antagonist, BHV-2100, in the acute treatment of migraine. The study is a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of two doses (75 mg and 150 mg) of BHV-2100 in the acute treatment of migraine. The trial is designed to support registration with FDA-accepted co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours and is expected to enroll approximately 575 patients across 60 sites in the United States.

Public offering – On October 2, 2024, the Company closed its previously announced underwritten public offering of 6,052,631 of its common shares, which included the full exercise of the underwriters’ option to purchase additional shares, at the public offering price of $47.50 per share. The net proceeds raised in the offering, after deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $269.9M. As of November 8, 2024, we had 101,122,246 common shares outstanding.
Expected Upcoming Milestones:

We believe Biohaven is well positioned to achieve significant milestones in 2024 and 2025 across numerous programs:

Selective Kv7 Activator:

Continue 5 ongoing Phase 2/3 trials with BHV-7000 in focal epilepsy, idiopathic generalized epilepsy, MDD, and bipolar disorder
Troriluzole:

NDA submission to FDA on track for 4Q 2024, following release of pivotal topline results in SCA in September 2024
Two Phase 3 trials with troriluzole in OCD; expect to conduct interim analysis of the second Phase 3 OCD trial in 4Q 2024 and report topline data from first Phase 3 OCD trial in 1H 2025
Taldefgrobep alfa:

Report topline data from Phase 3 trial with taldefgrobep in SMA in 4Q 2024
Initiate Phase 2 trial with taldefgrobep in obesity in 4Q 2024 or early 2025
First-in-class TRPM3 Antagonist:

Continue advancing enrollment in Phase 2 trial with BHV-2100 in acute migraine and neuropathic pain (laser-evoked potential experimental pain paradigm)
TYK2/JAK1 Inhibitor:

Complete SAD/MAD studies with BHV-8000 and advance to Phase 2 in the coming months
MoDE Platform

Submit a total of 4 INDs in 2024
Continue to advance Phase 1 SAD and MAD studies with subcutaneous BHV-1300, with a further study update in 4Q 2024
Next Generation ADC Platform:

Advance Phase 1 Trop-2 directed program BHV-1510 in multiple tumor types
Capital Position:

Cash, cash equivalents, marketable securities and restricted cash as of October 2, 2024 totaled approximately $642 million, which includes net proceeds of $269.9 million from the public offering of 6,052,631 common shares completed on October 2, 2024.

Third Quarter 2024 Financial Highlights:

Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $157.6 million for the three months ended September 30, 2024, compared to $95.5 million for the three months ended September 30, 2023. The increase of $62.1 million was due to additional and advancing clinical trials, including late Phase 3 and Phase 2/3 studies, and preclinical research programs in 2024, as compared to the same period in the prior year. Non-cash share-based compensation expense was $7.2 million for the three months ended September 30, 2024, an increase of $5.0 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the third quarter of 2024, primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024.

General and Administrative (G&A) Expenses: G&A expenses were $20.6 million for the three months ended September 30, 2024, compared to $15.0 million for the three months ended September 30, 2023. The increase of $5.5 million was partly due to increased non-cash share-based compensation expense, which was $5.0 million for the three months ended September 30, 2024, an increase of $2.7 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the third quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024.

Other Income, Net: Other income, net was $17.8 million for the three months ended September 30, 2024, compared to other income, net of $4.7 million for the three months ended September 30, 2023. The increase of $13.1 million was primarily due to non-cash changes in the fair value of our derivative liabilities recorded in connection with the amendment to our Membership Interest Purchase Agreement with Knopp Biosciences LLC in May 2024 (the Knopp Amendment), as well as increased investment income, partially offset by changes in the fair value of our forward contract liability recorded in connection with the Knopp Amendment.

Net Loss: Biohaven reported a net loss for the three months ended September 30, 2024 of $160.3 million, or $1.70 per share, compared to $102.6 million, or $1.50 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended September 30, 2024 was $164.1 million, or $1.74 per share, compared to $98.1 million, or $1.44 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below.

Non-GAAP Financial Measures
This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, which are adjusted to exclude non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, and changes in the fair value of derivative liabilities, which do not correlate to actual cash payment obligations in the relevant periods. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. However, Biohaven believes the presentation of non-GAAP adjusted net loss and adjusted net loss per share, when viewed in conjunction with GAAP results, provides investors with a more meaningful understanding of ongoing operating performance and can assist investors in comparing Biohaven’s performance between periods.

In addition, these non-GAAP financial measures are among those indicators Biohaven uses as a basis for evaluating performance, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this news release.

On November 12, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported positive topline results from the relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML) cohort in the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib, an oral, small molecule menin inhibitor (Press release, Syndax, NOV 12, 2024, View Source [SID1234648212]).

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The primary endpoint was met with a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23% (15/64; 95% confidence interval [CI]: 14%, 36%; one-sided p-value =0.0014) among the efficacy evaluable adults with R/R mNPM1 AML in the Phase 2 portion of the AUGMENT-101 trial. Among the patients who achieved CR/CRh, 12 patients had a CR and three had a CRh. The observed median duration of CR/CRh responses was 4.7 months (95% CI: 1.2, 8.2) at the time of the data cutoff with three patients remaining in response. Minimal residual disease (MRD) status was assessed in 14 of 15 patients who achieved CR/CRh, 64% (9/14) of whom were MRD negative. The overall response rate (ORR)1 was 47% (30/64; 95% CI: 34%, 60%). 17% (5/30) of patients who achieved an overall response underwent hematopoietic stem cell transplant (HSCT) following treatment with revumenib, with three resuming revumenib therapy post-transplant.

"We are thrilled to report positive pivotal data in R/R mNPM1 AML patients treated with revumenib, which has shown compelling and notably consistent results across treatment settings for both mNPM1 AML and KMT2A-rearranged acute leukemias," said Michael A. Metzger, Chief Executive Officer of Syndax. "With the anticipated FDA approval of revumenib for the treatment of R/R KMT2A-rearranged acute leukemias this quarter, and this second positive pivotal data readout, we are well-positioned to meaningfully impact the estimated 40% of AML patients with these two genetic alterations."

The AUGMENT-101 Phase 2 protocol-defined efficacy evaluable population included 64 adult patients with R/R mNPM1 AML. The median age was 65 (range: 19, 84). Patients were heavily pretreated, with 36% having received three or more prior lines of therapy (median prior lines: 2) and 75% of patients previously treated with venetoclax.

The safety population included 84 adult and pediatric patients with R/R mNPM1 AML in the Phase 2 portion of the AUGMENT-101 trial. The safety profile observed with revumenib in this population was consistent with previously reported data. Treatment-related adverse events (TRAEs) leading to treatment discontinuations were 5% (4/84). TRAEs of Grade ≥3 in more than 10% of patients included: QTc prolongation (21%), anemia (14%), febrile neutropenia (13%), differentiation syndrome (13%), and platelet count decreased (11%). Grade 3 treatment-related DS was observed in 11% (9/84) of patients while 2% (2/84) experienced Grade 4 DS and no patients experienced Grade 5. Grade 3 treatment-related QTc prolongation was observed in 19% (16/84) of patients while 2% (2/84) experienced Grade 4 QTc prolongation and no patients experienced Grade 5.

"Relapsed or refractory mNPM1 AML is a very challenging disease with a poor prognosis and an urgent need for new treatments," said Eytan M. Stein, M.D., Chief, Leukemia Service, Memorial Sloan Kettering Cancer Center. "The positive results for revumenib in this heavily pre-treated population, which included more than 75% who previously failed venetoclax, are very encouraging. In particular, the robust rates of overall response, including deep molecular remissions and low discontinuation rates, highlight the tremendous promise of revumenib in the treatment of R/R mNPM1 AML patients."

Revumenib Near-Term Milestones

The Company has several trials of revumenib ongoing across the treatment landscape in mNPM1 and KMT2A-rearranged (KMT2Ar) acute leukemias. In addition to the clinical trials that Syndax is conducting, the Company is working with cooperative groups and key investigators to further elucidate the potential clinical benefit of revumenib. Syndax expects to achieve the following upcoming revumenib milestones:

Receive FDA approval for treatment of R/R KMT2Ar acute leukemias in the fourth quarter of 2024.
Present data in KMT2Ar and mNPM1 acute leukemias at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024.
Initiate a pivotal combination trial with venetoclax/azacitidine in newly diagnosed mNPM1 AML or KMT2Ar acute leukemias by year-end 2024.
Publish pivotal AUGMENT-101 results in R/R mNPM1 AML patients and present results at a medical conference in the first half of 2025.
Submit a supplemental NDA (sNDA) for treatment of R/R mNPM1 AML in the first half of 2025.
Conference Call and Webcast
Syndax will host a conference call and webcast to discuss the results of the AUGMENT-101 trial in R/R mNPM1 AML today, November 12, 2024, at 8:00 a.m. ET.

The live webcast may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following:

Conference ID: Syndax Conference Call 1
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast: https://www.veracast.com/webcasts/syndax/events/specialconf1.cfm

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call.

About Revumenib
Revumenib is an oral, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML), and mutant NPM1 AML. The Journal of Clinical Oncology published results from the Phase 2 AUGMENT-101 trial of revumenib in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About the Phase 1/2 AUGMENT-101 Trial
AUGMENT-101 an open-label, multi-center trial evaluating the safety, tolerability, pharmacokinetics, and efficacy of revumenib that consists of a dose escalation part and an expansion part. In the dose escalation part, a revumenib dose with and without a strong CYP3A4 inhibitor was identified. The expansion part was designed to evaluate revumenib in patients with relapsed or refractory (R/R) KMT2Ar AML, patients with KMT2Ar ALL, and patients with mutant NPM1 (mNPM1) AML. The primary endpoint for each of the cohorts is efficacy as measured by the rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) and short- and long-term safety and tolerability, with secondary endpoints including duration of response (DOR) and overall survival (OS).

More information can be found on www.clinicaltrials.gov (NCT04065399).

Positive data from the KMT2Ar AML and ALL patients in the trial supported a New Drug Application (NDA) filing for revumenib in R/R KMT2Ar acute leukemia, which is currently under review by the U.S. FDA with a PDUFA action date of December 26, 2024. Positive data from the mNPM1 AML patients in the trial are expected to support an sNDA filing in the first half of 2025.

About Mutant NPM1 (mNPM1) Acute Myeloid Leukemia (AML)
Mutations in the NPM1 gene are the most common genetic alteration in adult AML and are observed in approximately 30% of cases. Patients with relapsed or refractory mNPM1 AML have a poor prognosis and high unmet need. Similar to KMT2A-rearranged acute leukemia, mNPM1 AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. mNPM1 AML is routinely diagnosed through currently available screening techniques. There are currently no approved targeted therapies for mNPM1 AML.

On November 12, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported financial results for the third quarter of 2024 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, NOV 12, 2024, View Source [SID1234648211]).

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"In the third quarter, we continued to see robust growth in the U.S. launch of OGSIVEO for adults with desmoid tumors. As we approach nearly one full year on market, we are very encouraged by the metrics we are seeing regarding the breadth of physician prescribing, the number of patients on OGSIVEO, and the number of patients identified who may stand to benefit in the future from our medicine. We were also very pleased to receive Priority Review on our NDA for mirdametinib in NF1-PN this quarter, which positions us to potentially have a second approved medicine in early 2025," said Saqib Islam, Chief Executive Officer of SpringWorks. "Our focus for the remainder of the year is to continue building on OGSIVEO’s momentum in the U.S. while working to also bring it to patients in Europe, to advance our commercial preparations for mirdametinib in anticipation of serving patients with NF1-PN in the U.S. and Europe, and to progress our emerging portfolio."

Recent Business Highlights and Upcoming Milestones

OGSIVEO (Nirogacestat)

Continued strong commercial execution of the OGSIVEO launch, with net product revenue of $49.3 million in the third quarter of 2024, representing a 23% increase over the second quarter of 2024.
In September, more than 800 unique desmoid tumor patients filled an OGSIVEO script. As of the end of the third quarter of 2024, approximately 420 treatment centers have ordered OGSIVEO since approval and approximately 65 percent of OGSIVEO patients on OGSIVEO are receiving the product in the 150 mg or 100 mg tablets blister packages. SpringWorks expects to complete the full transition to blister packages by the end of the year. In addition, through August 2024, approximately 10,000 unique desmoid tumor patients have been identified through the new desmoid tumor ICD-10 diagnostic code since the introduction of the code in October 2023.
A Marketing Authorization Application (MAA) for nirogacestat for the treatment of adult patients with desmoid tumors is under review with the European Medicines Agency (EMA).
Long-term follow-up data from the Phase 3 DeFi trial of nirogacestat in adults with progressing desmoid tumors will be presented as a late-breaking oral presentation at the upcoming Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting. These results, utilizing an August 2024 data cutoff date, showed that longer-term treatment with nirogacestat (median duration of treatment: 34 months) was associated with further reductions in tumor size, increase in objective response rate with additional partial responses and complete responses, sustained improvements in desmoid tumor symptoms including pain, and a consistent safety profile compared to the April 2022 data cutoff date for the primary results of the trial.
SpringWorks expects to report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with recurrent ovarian granulosa cell tumors in the first half of 2025.
SpringWorks is continuing to support several industry and academic collaborator studies evaluating nirogacestat as part of B-cell maturation antigen (BCMA) combination therapy regimens across treatment lines in patients with multiple myeloma.
Mirdametinib

SpringWorks’ New Drug Application (NDA) for mirdametinib for the treatment of children and adults with NF1-PN was granted Priority Review by the U.S. Food and Drug Administration (FDA) and assigned a Prescription Drug User Fee Act (PDUFA) action date of February 28, 2025.
SpringWorks’ MAA for mirdametinib for the treatment of children and adults with NF1-PN was validated by the EMA and is currently under review.
Results from the Phase 2b ReNeu trial were published in the Journal of Clinical Oncology.
Additional data from the pediatric and adult cohorts of the Phase 2b ReNeu trial will be presented in oral and poster presentations at the 2024 Society for Neuro-Oncology (SNO) meeting. Data demonstrate that the deep responses in tumor volume reduction seen in ReNeu were achieved regardless of age, sex, target PN volume at baseline, tumor location, or progression status at baseline and suggest a trend between deep response and earlier achievement of a first confirmed response. Patients with deep responses also had a trend of longer treatment duration. In addition, adults and children with NF1-PN had clinically meaningful, early, and sustained improvement in health-related quality of life over the course of mirdametinib treatment.
Data from the Phase 1/2 trial evaluating mirdametinib in pediatric and young adult patients with low-grade gliomas (LGG) are being presented in an oral presentation at the 2024 SNO meeting. Results from 23 patients enrolled in the Phase 1 portion of the study suggested that mirdametinib, which has shown high blood brain barrier penetration, has encouraging clinical activity in patients with recurrent/progressive LGG across a variety of MAPK pathway aberrations. Twelve (63%) of the 19 patients with measurable tumors achieved an objective response (one major, six partial, and five minor responses). The Phase 2 portion of the study is ongoing and recruiting patients.
Emerging Pipeline

A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the second half of 2025. Brimarafenib is an investigational, selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, Ltd.
Several combination therapy oncology programs are ongoing: a Phase 1/2a study of brimarafenib and mirdametinib in MAPK mutant solid tumors, a Phase 1b trial of brimarafenib and Amgen’s EGFR inhibitor, panitumumab, in colorectal and pancreatic cancer patients with known MAPK pathway mutations, and a Phase 1b trial of mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with NRAS mutant solid tumors.
In October, SpringWorks presented preclinical data at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) symposium on Molecular Targets and Cancer therapeutics demonstrating the utility of SW-682 as a monotherapy and in combination with mirdametinib in subsets of head and neck cancer as well as in combination with KRAS G12C inhibitors in KRAS G12C mutant NSCLC. SW-682 is an investigational novel, oral, potent, and selective pan-TEAD inhibitor and patients are being enrolled in a Phase 1a trial in Hippo-mutant solid tumors.
General Corporate

In July, SpringWorks appointed Martin Mackay, Ph.D. to the Company’s Board of Directors. Dr. Mackay is a highly accomplished R&D executive with more than 30 years of pharmaceutical and biotech R&D experience, including leadership roles at Pfizer, AstraZeneca and Alexion.
Third Quarter 2024 Financial Results

Product Revenue: OGSIVEO net product revenue was $49.3 million in the third quarter of 2024.
Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $61.6 million for the third quarter of 2024, compared to $46.5 million for the comparable period of 2023. The increase in SG&A expense was primarily attributable to commercial readiness activities to support the U.S. launch of mirdametinib, if approved.
Research and Development (R&D) Expenses: R&D expenses were $42.3 million for the third quarter of 2024, compared to $37.5 million for the comparable period of 2023. The increase in R&D expenses was primarily attributable to an increase in costs related to drug manufacturing, clinical trials, other research, consulting and professional services.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $53.5 million, or $0.72 per share, for the third quarter of 2024. This compares to a net loss of $79.4 million, or $1.27 per share, for the comparable period of 2023.
Cash, Cash Equivalents, and Marketable Securities: Cash, cash equivalents and marketable securities were $498.1 million as of September 30, 2024. SpringWorks expects this cash position to fund the Company through profitability, which is expected in the first half of 2026.
Conference Call Information

SpringWorks will host a conference call and webcast today, Tuesday, November 12, at 8:30 a.m. ET to review its third quarter 2024 financial results and discuss recent business updates. To join the live webcast and view the corresponding slides, please click here. To access the live call by phone, please pre-register for the call by clicking here. Once registration is complete, participants will be provided with a dial-in number and conference code to access the call. A replay of the webcast will be available for a limited time following the event on the Investors and Media section of the Company’s website at View Source

On November 12, 2024 Schrödinger, Inc. (Nasdaq: SDGR) reported financial results for the third quarter of 2024 and provided a business update (Press release, Schrodinger, NOV 12, 2024, View Source [SID1234648210]). In a separate press release issued earlier today, Schrödinger announced a multi-target research and licensing collaboration with Novartis. Under the terms of the agreement, Novartis will pay Schrödinger $150 million upfront, and Schrödinger will also be eligible to receive up to $2.3 billion in milestone payments. Schrödinger also announced an expanded three-year software agreement that substantially increases Novartis’s access to Schrödinger’s computational predictive modeling technology and enterprise informatics platform.

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"We have continued to make important advances across our business this year. Recent progress, including the collaboration with Novartis and milestones achieved by our co-founded companies underscore the strength of our business model," said Ramy Farid, Ph.D., chief executive officer of Schrödinger. "While our third quarter software revenue was slightly below our expectations, we are excited about the opportunities we have in the fourth quarter to drive software growth through increasing utilization among our customers. Our proprietary pipeline is progressing, and we look forward to sharing the initial Phase 1 data from each of our three lead programs next year."

Third Quarter 2024 Financial Results
•Total revenue for the third quarter was $35.3 million, compared to $42.6 million in the third quarter of 2023.
•Software revenue for the third quarter increased 10% to $31.9 million, compared to $28.9 million in the third quarter of 2023. The increase was due to the growing contribution of hosted licenses, partially offset by multi-year on-premise contracts signed in the third quarter of 2023.
•Drug discovery revenue was $3.4 million for the third quarter, compared to $13.7 million in the third quarter of 2023. The third quarter of 2023 included accelerated recognition of deferred revenue associated with programs no longer in the company’s collaborative portfolio.
•Software gross margin decreased to 73% for the third quarter, compared to 76% in the third quarter of 2023, reflecting lower profitability of revenue associated with the predictive toxicology initiative.
•Operating expenses were $86.2 million for the third quarter, compared to $79.8 million for the third quarter of 2023. The increase was primarily due to higher R&D expenses.
•Other income, which includes changes in fair value of equity investments and interest income, was $30.2 million for the third quarter, compared to other expense of $8.7 million for the third quarter of 2023, primarily reflecting changes in fair value of the company’s equity investments.
•Net loss for the third quarter was $38.1 million, compared to net loss of $62.0 million in the third quarter of 2023.
•At September 30, 2024, Schrödinger had cash, cash equivalents, restricted cash and marketable securities of $398.4 million, compared to $468.8 million at December 31, 2023.

Three Months Ended
September 30,
2024 2023 % Change
(in millions)
Total revenue $ 35.3 $ 42.6 (17)%
Software revenue 31.9 28.9 10%
Drug discovery revenue 3.4 13.7 (75)%
Software gross margin 73 % 76 %
Operating expenses $ 86.2 $ 79.8 7.9%
Other income (expense) $ 30.2 $ (8.7) —
Net loss $ (38.1) $ (62.0) —

For the three and nine months ended September 30, 2024, Schrödinger reported non-GAAP net losses of $63.7 million and $174.2 million, respectively, compared to non-GAAP net losses of $50.4 million and $134.8 million for the three and nine months ended September 30, 2023. A reconciliation of non-GAAP net loss to GAAP net (loss) income can be found in "Non-GAAP Information" and financial tables below.

2024 Financial Outlook
Today Schrödinger updated its 2024 full-year financial guidance. The company’s updated financial expectations for the fiscal year ending December 31, 2024, are as follows:
•Software revenue growth is now expected to range from 8% to 13%.
•Drug discovery revenue is now expected to range from $20 million to $30 million.
•Software gross margin is expected to be slightly lower than 2023 and in the range of 2022 based on the effect of the research grant from the Bill & Melinda Gates Foundation.
•Operating expense growth in 2024 is expected to range from 8% to 10%.
•Cash used for operating activities in 2024 is expected to be above cash used for operating activities in 2023, depending on the timing of cash received from collaborations.

"We have increased the lower end of our software revenue growth guidance for the year, reflecting our confidence in the opportunities to meet our growth goals and the continued enthusiasm for the deployment of computation in drug discovery across the industry," stated Geoff Porges, MBBS, chief financial officer of Schrödinger. "Collaborations continue to be an important element of our business model, and we are pleased Novartis has recognized the value of our platform and the capabilities of our team with this agreement. This quarter we added $48 million to our cash balance as a result of Lilly’s acquisition of Morphic and expect to add even more capital from the payments associated with the collaboration announced today."

Recent Highlights
Collaborators, Partners, and Co-Founded Companies
•Today Schrödinger announced a multi-target research and licensing collaboration and expanded software licensing agreement with Novartis. The collaboration agreement is intended to advance multiple development candidates into Novartis’s portfolio for further development and commercialization. Under the terms of the agreement, Novartis will pay Schrödinger $150 million upfront, and Schrödinger will also be eligible to receive up to $892 million in research, development and regulatory milestone payments. Additionally, Schrödinger is eligible for up to $1.38 billion in commercial milestones and tiered mid single-digit to low double-digit royalties on net sales of each product commercialized by Novartis. Schrödinger also announced an expanded three-year software agreement that substantially increases Novartis’s access to Schrödinger’s computational predictive modeling technology and enterprise informatics platform.

•In November, Nimbus Therapeutics, a company co-founded by Schrödinger, announced updated data from its Phase 1/2 clinical study of NDI-101150 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. NDI-101150 is a HPK1 inhibitor in development for the treatment of solid tumors.

•In October, Ajax Therapeutics, a company co-founded by Schrödinger, announced the dosing of the first patient in the Phase 1 study of AJ1-11095, a novel JAK2 inhibitor, in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocytopenia myelofibrosis.

•In August, Lilly completed its acquisition of Morphic, a company co-founded by Schrödinger, at the announced acquisition price of $57 per share, or approximately $3.2 billion. Schrödinger tendered 834,968 shares for an aggregate of $47.6 million in cash. Schrödinger remains entitled to low single-digit royalties on acquired Morphic clinical development programs, including MORF-057.

Proprietary Pipeline
•In October, Schrödinger presented preclinical data on SGR-3515, its Wee1/Myt1 inhibitor, at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (ENA 2024). The data demonstrated that SGR-3515 had a favorable pharmacological profile and dosing schedule that supports evaluating intermittent dosing in patients.

•In October, Schrödinger presented preclinical data from the company’s discovery-stage PRMT5 program at ENA 2024. The poster reviewed the discovery of a series of highly selective PRMT5-MTA inhibitors, following the use of Schrödinger’s computational platform to identify a novel molecular series with potential for best-in-class pharmacological properties.

•Schrödinger continues to advance SGR-1505, its MALT1 inhibitor, through the Phase 1 dose-escalation study in patients with relapsed/refractory B-cell malignancies. The company expects to report initial clinical data from this study in the first half of 2025.

•SGR-2921, the company’s CDC7 inhibitor, is progressing through a Phase 1 dose-escalation study in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome. Schrödinger expects to report initial clinical data from this study in the second half of 2025.

•The Phase 1 study of SGR-3515 continues to enroll patients with advanced solid tumors at sites in the U.S. and Canada. Initial clinical data from this study is expected in the second half of 2025.

Platform
•In the third quarter, Schrödinger scientists published five papers highlighting ongoing research to advance the platform, including a method for treating significant conformational changes in free energy simulations of protein-ligand binding, a model of coarse grained simulation of mRNA-loaded lipid nanoparticle self-assembly, and a review of recent developments and unique features in its quantum mechanics software package.

Webcast and Conference Call Information
Schrödinger will host a conference call to discuss its third quarter 2024 financial results and the recently announced Novartis collaboration on Tuesday, November 12, 2024, at 8:00 a.m. ET. The live webcast can be accessed under "News & Events" in the investors section of Schrödinger’s website, View Source To participate in the live call, please register for the call here. It is recommended that participants register at least 15 minutes in advance of the call. Once registered, participants will receive the dial-in information. The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

On November 12, 2024 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of oncolytic immunotherapies, reported financial results for the fiscal second quarter ended September 30, 2024 and provided a business update (Press release, Replimune, NOV 12, 2024, View Source [SID1234648209]).

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"I am incredibly proud of our progress as we rapidly approach the submission of our BLA for RP1," said Sushil Patel, Ph.D., CEO of Replimune. "The IGNYTE data was presented at major medical meetings and was well received by the oncology community, who noted the importance of the systemic activity demonstrated and the continuing need for additional treatments for patients with advanced melanoma. As a team, we have been focused on our ongoing preparation for commercialization, including building our field teams, completing important market research and developing our market access teams, among many other activities to ensure we are well positioned to reach as many physicians and patients as possible."

Program Highlights & Milestones

RP1

RP1 combined with Opdivo (nivolumab) in anti-PD1 failed melanoma
In September, the Company completed a pre-BLA meeting with the FDA confirming plans to submit a BLA for RP1 for the treatment of anti-PD1 failed melanoma via the accelerated approval pathway before the end of the year.
The IGNYTE-3 confirmatory trial of RP1 in advanced melanoma is underway with first patient enrolled in August. This clinical trial is a 2-arm randomized Phase 3 trial with a defined list of physician’s choice treatment options as the comparator arm in advanced melanoma patients who progressed on anti-PD1 and anti-CTLA-4 therapy or are ineligible for anti-CTLA-4 treatment.
Late-breaking abstracts presented at ESMO (Free ESMO Whitepaper) and SITC (Free SITC Whitepaper) shared the primary analysis from the IGNYTE trial.
The primary analysis reiterated the positive top line results presented in June and confirmed the 12-month overall response rate was 33.6% by modified RECIST 1.1 criteria, the primary endpoint as defined in the protocol, and 32.9% by RECIST 1.1 criteria, an additional analysis requested by the FDA.
In addition, new data shared showed activity across all clinical subgroups, including patients who had prior anti-PD1 and anti-CTLA-4 (ORR 27.7%) and for those who had primary resistance to anti-PD1 (ORR 35.9%) by modified RECIST 1.1.
Median duration of response from response initiation was 21.6 months and median duration of response from treatment initiation was 27.6 months.
Initial biomarker data shows increased CD8+ T cell and PD-L1 expression post treatment in 50% of the tested biopsies. The increase in gene expression signature, associated CD8+ T cells and inflammatory cytokines further highlight the potential of RP1 plus nivolumab to generate a potent anti-tumor response.
RP2

RP2 in Uveal Melanoma
Study start-up activities are underway for a registration-directed study of RP2 in metastatic uveal melanoma in patients who are immune checkpoints inhibitor-naïve. The study plans to enroll the first patient in a randomized trial of RP2 in combination with nivolumab vs. ipilimumab and nivolumab, or nivolumab for those ineligible for ipilimumab in the first quarter of 2025.
RP2 in hepatocellular carcinoma (HCC)
A Phase 2 clinical trial with RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is actively screening patients.
Financial Highlights

Cash Position: As of September 30, 2024, cash, cash equivalents and short-term investments were $432.1 million, as compared to $420.7 million as of fiscal year ended March 31, 2024. The increase in cash balance was directly related to the PIPE financing in June, offset by cash utilized in operating activities in advancing the Company’s clinical development plans.
Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of September 30, 2024 will enable the Company to fund operations into the second half of 2026 which includes scale up for the commercialization of RP1 in skin cancers and for working capital and general corporate purposes.

R&D Expenses: Research and development expenses were $43.4 million for the fiscal second quarter ended September 30, 2024, as compared to $49.1 million for the fiscal second quarter ended September 30, 2023. This decrease was primarily due to the wind down of the CERPASS and IGNYTE Phase II studies, as well as the deprioritization of development efforts on RP3. Research and development expenses included $4.1 million in stock-based compensation expenses for the fiscal second quarter ended September 30, 2024.
S,G&A Expenses: Selling, general and administrative expenses were $15.5 million for the fiscal second quarter ended September 30, 2024, as compared to $14.7 million for the fiscal second quarter ended September 30, 2023. Selling, general and administrative expenses included $4.6 million in stock-based compensation expenses for the fiscal second quarter ended September 30, 2024.
Net Loss: Net loss was $53.1 million for the fiscal second quarter ended September 30, 2024, as compared to a net loss of $60.0 million for the fiscal second quarter ended September 30, 2023.
About RP1

RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2

RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.