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.

On November 12, 2024-Equillium Inc. (Nasdaq: EQ), a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders, reported that a poster was presented over the weekend at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Equillium, NOV 12, 2024, View Source [SID1234648207]). The conference took place at the George R. Brown Convention Center in Houston, Texas from November 6 to 10, 2024.

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"These data provide deeper insights into the dual and synergistic signaling of IL-15 and IL-21 that drives aggressive T and NK cell responses that promote the cytolytic activity and interferon gamma production observed in multiple inflammatory diseases," said Dr. Stephen Connelly, chief scientific officer at Equillium. "As such, in the context of treating inflammatory disease, or augmenting anti-tumor responses, it would be optimal to inhibit or activate both cytokines in a single agent and is a focus of the multi-cytokine platform at Equillium."

Title: Interleukin (IL)-15 and IL-21 synergistically enhance NK and CD8+ T cell responses
Presenting Author: Phoi Tiet, Senior Research Associate, Equillium, Inc.
Poster Number: 908

Key Highlights, Summaries & Conclusions from Presentation:

Synergistic signaling of IL-15 and IL-21 enhanced markers of activity including CD25, PD-1, Tim-3 and ICOS, in addition to increased production of granzyme A, granzyme B and perforin, indicating that these two cytokines play important roles in activation, development, and survival of NK and CD8+ T cells.
IL-15 and IL-21 cooperatively amplified CD8+T and NK cytolytic activities and IFNγ production, suggesting that targeting these two pathways can amplify cell-based immunity.
Preliminary evaluation of IL-15 and IL-21 in an antigen-based T cell exhaustion model described here suggests that the combination of the two cytokines has a modest effect on reversing the phenotype and function of terminally exhausted CD8+ T cells as shown by the increase in the percentage of TCF-1 positive cells, decrease in the percentage of TOX positive cells, and increase the percentage of polyfunctional cells.
These results indicate that the combination of IL-15 and IL-21 robustly augments NK and CD8 T cell activity. The ability to not only boost cytolytic function of naïve and effector cells but to partially rescue the exhausted phenotype of cytotoxic CD8+ T cells is a promising therapeutic approach and addresses the challenges of immuno-oncology.
The poster presentation is available under the Multi-Cytokine Inhibition tab on the Presentations page of the Technology section on the corporate website.

About Multi-Cytokine Platform and Multi-Cytokine Inhibitors EQ101 & EQ302

Our proprietary multi-cytokine platform generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. This approach is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as Janus kinase inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune and inflammatory diseases.

Current platform assets include EQ101, a clinical stage, first-in-class, selective, tri-specific inhibitor of IL-2, IL-9, and IL-15 for intravenous and subcutaneous delivery and EQ302, a preclinical stage, first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for oral delivery.

On November 12, 2024 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported financial results for the third quarter and nine months ended September 30, 2024 (Press release, RAPT Therapeutics, NOV 12, 2024, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-reports-third-quarter-2024-financial-results [SID1234648208]).

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Financial Results for the Third Quarter and Nine Months Ended September 30, 2024

Third Quarter Ended September 30, 2024

Net loss for the third quarter of 2024 was $18.4 million, compared to $31.4 million for the third quarter of 2023.

Research and development expenses for the third quarter of 2024 were $13.3 million, compared to $27.0 million for the same period in 2023. The decrease in research and development expenses was primarily due to lower development costs related to zelnecirnon, tivumecirnon and early stage programs, as well as decreased expenses for personnel, consultants and lab supplies.

General and administrative expenses for the third quarter of 2024 were $6.4 million, compared to $6.9 million for the same period in 2023. The decrease in general and administrative expenses was primarily due to decreased expenses for personnel, consultants and insurance premiums, partially offset by increases in expenses for non-cash stock-based compensation and facilities.

On July 16, 2024, the Company’s board of directors approved a reduction of the Company’s workforce to conserve cash resources. The workforce reduction affected 47 people, or approximately 40% of the Company’s headcount. The Company incurred $0.9 million in restructuring charges in connection with the workforce reduction, consisting of cash-based expenses related to employee severance payments, benefits and related costs. The Company completed the workforce reduction plan and all the related cash payments during the third quarter ended September 30, 2024.

Nine Months Ended September 30, 2024

Net loss for the nine months ended September 30, 2024 was $76.6 million, compared to $85.9 million for the same period in 2023.

Research and development expenses for the nine months ended September 30, 2024 were $60.8 million, compared to $74.2 million for the same period in 2023. The decrease in research and development expenses was primarily due to decreases in development costs related to zelnecirnon, tivumecirnon and early-stage programs, as well as lab supplies, partially offset by increased expenses for personnel, consultants, facilities and non-cash stock-based compensation.

General and administrative expenses for the nine months ended September 30, 2024 were $20.9 million, compared to $19.6 million for the same period in 2023. The increase in general and administrative expenses was primarily due to increased expenses for personnel, non-cash stock-based compensation and facilities, partially offset by decreases in expenses for consultants and insurance premiums.

As of September 30, 2024, the Company had cash and cash equivalents and marketable securities of $97.9 million.

On November 12, 2024 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported financial results for the third quarter and nine months ended September 30, 2024 (Press release, RAPT Therapeutics, NOV 12, 2024, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-reports-third-quarter-2024-financial-results [SID1234648208]).

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Financial Results for the Third Quarter and Nine Months Ended September 30, 2024

Third Quarter Ended September 30, 2024

Net loss for the third quarter of 2024 was $18.4 million, compared to $31.4 million for the third quarter of 2023.

Research and development expenses for the third quarter of 2024 were $13.3 million, compared to $27.0 million for the same period in 2023. The decrease in research and development expenses was primarily due to lower development costs related to zelnecirnon, tivumecirnon and early stage programs, as well as decreased expenses for personnel, consultants and lab supplies.

General and administrative expenses for the third quarter of 2024 were $6.4 million, compared to $6.9 million for the same period in 2023. The decrease in general and administrative expenses was primarily due to decreased expenses for personnel, consultants and insurance premiums, partially offset by increases in expenses for non-cash stock-based compensation and facilities.

On July 16, 2024, the Company’s board of directors approved a reduction of the Company’s workforce to conserve cash resources. The workforce reduction affected 47 people, or approximately 40% of the Company’s headcount. The Company incurred $0.9 million in restructuring charges in connection with the workforce reduction, consisting of cash-based expenses related to employee severance payments, benefits and related costs. The Company completed the workforce reduction plan and all the related cash payments during the third quarter ended September 30, 2024.

Nine Months Ended September 30, 2024

Net loss for the nine months ended September 30, 2024 was $76.6 million, compared to $85.9 million for the same period in 2023.

Research and development expenses for the nine months ended September 30, 2024 were $60.8 million, compared to $74.2 million for the same period in 2023. The decrease in research and development expenses was primarily due to decreases in development costs related to zelnecirnon, tivumecirnon and early-stage programs, as well as lab supplies, partially offset by increased expenses for personnel, consultants, facilities and non-cash stock-based compensation.

General and administrative expenses for the nine months ended September 30, 2024 were $20.9 million, compared to $19.6 million for the same period in 2023. The increase in general and administrative expenses was primarily due to increased expenses for personnel, non-cash stock-based compensation and facilities, partially offset by decreases in expenses for consultants and insurance premiums.

As of September 30, 2024, the Company had cash and cash equivalents and marketable securities of $97.9 million.