On February 26, 2025 Schrödinger, Inc. (Nasdaq: SDGR) reported financial results for the fourth quarter and full-year ended December 31, 2024, and provided its financial outlook for 2025 (Press release, Schrodinger, FEB 26, 2025, View Source [SID1234650640]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are delighted with Schrödinger’s excellent financial performance in 2024. Software revenue growth exceeded our expectations, showing the resilience of our business through changing industry cycles and the impact of large contract renewals. Our drug discovery collaboration portfolio is expanding, driven by our new agreement with Novartis and expanded collaborations with Otsuka and Lilly, and we expect to report initial clinical data from our three lead proprietary programs this year," said Ramy Farid, Ph.D., chief executive officer of Schrödinger. "We continue to see increasing momentum and conviction around our validated computational methods and are committed to remaining scientific leaders in this area. With our platform, our collaborations, our programs, and our strong financial position, we believe we are well positioned to deliver across all facets of our business in 2025 and beyond."

Today Schrödinger also announced that it has expanded its research collaboration with Eli Lilly and Company. This expansion builds on the companies’ previously announced collaboration, with the addition of an undisclosed target. The terms of the expanded collaboration are consistent with the previously announced agreement.

Fourth Quarter 2024 Financial Results
•Total revenue for the fourth quarter increased 19.1% to $88.3 million, compared to $74.1 million in the fourth quarter of 2023.
•Software revenue for the fourth quarter increased 16.0% to $79.7 million, compared to $68.7 million in the fourth quarter of 2023. The increase was primarily due to increased hosted revenue from large customers with additional contribution from new multi-year customer agreements.
•Drug discovery revenue was $8.7 million for the fourth quarter, compared to $5.5 million in the fourth quarter of 2023. The increase was primarily due to the recognition of milestones during the quarter.
•Software gross margin decreased to 83% for the fourth quarter, compared to 87% in the fourth quarter of 2023, primarily reflecting higher cost of revenue associated with the predictive toxicology initiative.
•Operating expenses were $84.8 million for the fourth quarter, compared to $87.2 million for the fourth quarter of 2023.
•Other expense, which includes changes in fair value of equity investments and interest income/expense, was $18.5 million for the fourth quarter, compared to $1.9 million for the fourth quarter of 2023.
•Net loss for the fourth quarter was $40.2 million, compared to $30.7 million in the fourth quarter of 2023.

Three Months Ended
December 31,
2024 2023 % Change
(in millions)
Total revenue $ 88.3 $ 74.1 19%
Software revenue 79.7 68.7 16%
Drug discovery revenue 8.7 5.5 58%
Software gross margin 83 % 87 %
Operating expenses $ 84.8 $ 87.2 (2.7)%
Other expense $ (18.5) $ (1.9) —
Net loss $ (40.2) $ (30.7) —

Full Year 2024 Financial Results
•Total revenue for the full year decreased 4.2% to $207.5 million, compared to $216.7 million for 2023.
•Software revenue for the full year increased 13.3% to $180.4 million, compared to $159.1 million for 2023. Revenue growth was primarily driven by increases in hosted contracts and contribution revenue.
•Drug discovery revenue for the full year was $27.2 million compared to $57.5 million for 2023. The first quarter of 2023 included the recognition of a $25 million milestone from BMS.
•Software gross margin was 80% for the full year, compared to 81% for 2023.
•Operating expenses were $341.4 million for the full year, compared to $318.1 million for 2023, primarily due to higher research and development expenses.
•Other income, which includes gains/loss on equity investments, changes in fair value of such investments and interest income/expense, was $23.6 million for the full year, compared to $220.4 million for 2023.
•Net loss for the full year was $187.1 million, compared to income of $40.7 million for 2023.
•At December 31, 2024, Schrödinger had cash, cash equivalents, restricted cash and marketable securities of approximately $367.5 million, compared to approximately $398.4 million at September 30, 2024 and approximately $468.8 million at December 31, 2023. In January 2025, Schrodinger received the $150 million upfront payment from Novartis for the recently announced drug discovery collaboration.

Twelve Months Ended
December 31,
2024 2023 % Change
(in millions)
Total revenue $ 207.5 $ 216.7 (4.2)%
Software revenue 180.4 159.1 13%
Drug discovery revenue 27.2 57.5 (53)%
Software gross margin 80 % 81 %
Operating expenses $ 341.4 $ 318.1 7.3%
Other income $ 23.6 $ 220.4 —
Net (loss) income $ (187.1) $ 40.7 —

For the three months and year ended December 31, 2024, Schrödinger reported net losses of $40.2 million and $187.1 million, respectively, compared to a net loss of $30.7 million and net income of $40.7 million for the three months and year ended December 31, 2023, respectively.
For the three months and year ended December 31, 2024, Schrödinger reported non-GAAP net losses of $17.2 million and $191.4 million, respectively, compared to non-GAAP net losses of $23.0 million and $157.8 million

for the three months and year ended December 31, 2023, respectively. See "Non-GAAP Information" below and the table at the end of this press release for a reconciliation of non-GAAP net income (loss) to GAAP net income (loss).

Full Year 2024 Key Performance Indicators (KPIs)
Schrödinger today reported 2024 key performance indicators for both the software and drug discovery components of its business.

Software. Total annual contract value (ACV) increased 23.7% to $190.8 million, and the ACV of Top 10 customers increased 43% to $73.1 million. The number of customers with an ACV of at least $5 million increased from four to eight, and the number of customers with an ACV of at least $1 million increased from 27 to 31. Schrödinger’s customer retention rate among customers with an ACV of at least $500,000 was 100% and the number of such customers increased from 54 to 61.

Drug discovery. Schrödinger ended 2024 with 13 ongoing programs eligible for royalties, compared to 12 the previous year. For the year ended December 31, 2024, the number of collaborators since 2018 increased to 19.

Software KPI 2024 2023
Total annual contract value (ACV) $190.8 million $154.2 million
ACV of Top 10 customers $73.1 million $51.0 million
Number of customers with at least $5M in ACV 8 4
Number of customers with at least $1M in ACV 31 27
Number of customers with at least $500,000 in ACV 61 54
Number of customers with at least $100,000 in ACV 235 222
Customer retention rate with at least $500,000 in ACV 100% 98%
Customer retention with at least $100,000 in ACV 95% 92%
Number of active customers with ACV of at least $1,000 1,752 1,785

Drug Discovery KPI 2024 2023
Ongoing programs eligible for royalties 13 12
Number of collaborators since 2018 19 17

For additional information about the company’s KPIs, see "Operating Metrics" below.

2025 Financial Outlook
As of February 26, 2025, Schrödinger provided the following expectations for the fiscal year ending December 31, 2025:
•Software revenue growth is expected to range from 10% to 15%.
•Drug discovery revenue is expected to range from $45 million to $50 million.
•Software gross margin is expected to range from 74% to 75%.
•Operating expense growth in 2025 is expected to be less than 5%.
•Cash used for operating activities in 2025 is expected to be significantly lower than cash used for operating activities in 2024.

For the first quarter of 2025, software revenue is expected to range from $44 million to $48 million.

Key Highlights
Collaborative Pipeline & Co-Founded Companies
•Earlier today, the company announced an expanded research collaboration with Lilly. The expansion adds an undisclosed target to the companies’ previously announced collaboration under terms consistent with the existing agreement.

•In January, Schrödinger announced that its research collaboration with Novartis received antitrust regulatory clearance, and Schrödinger received the upfront payment of $150 million from Novartis in January 2025.

•Also in January, the company announced an expanded research collaboration agreement with Otsuka Pharmaceutical Co., Ltd. The expansion adds another undisclosed target to the collaboration under terms consistent with the existing agreement.
•In December, Ajax Therapeutics, a company co-founded by Schrödinger, presented an overview poster of its ongoing Phase 1 trial evaluating AJ1-11095 for the treatment of myelofibrosis at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

•Also in December, Structure Therapeutics, a company co-founded by Schrödinger, announced the selection of ACCG-2671, as its lead oral small molecule amylin receptor agonist for the treatment of obesity. Schrödinger collaborated with Structure on the discovery of ACCG-2671 and is entitled to milestones and low single-digit royalties on sales.

Proprietary Pipeline
•In January, the U.S. Food and Drug administration granted SGR-2921, the company’s CDC7 inhibitor, Orphan Drug Designation for the treatment of acute myeloid leukemia (AML). Schrödinger expects to present initial clinical data from the ongoing Phase 1 study of SGR-2921 in patients with AML and myelodysplastic syndrome (MDS) in the second half of 2025.

•Schrödinger continues to progress the Phase 1 clinical study of SGR-1505, the company’s MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies and expects to report initial clinical data from the trial in the second quarter of 2025.

•The Phase 1 study of SGR-3515, Schrödinger’s Wee1/Myt1 inhibitor, 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
•The company is continuing to advance the science underpinning its platform, including advancing its predictive toxicology initiative, further integrating physics and AI/ML into platform workflows, and expanding the applicability of the platform to new high-value areas, including biologics and drug formulations.

•In January, Schrödinger scientists published a paper assessing the accuracy of free-energy perturbation (FEP) in predicting relative binding energies of ligands to DNA and RNA targets. The assessment suggests FEP+ has sufficient accuracy to guide lead optimization in drug discovery programs targeting nucleic acids.

Webcast and Conference Call Information
Schrödinger will host a conference call to discuss its fourth quarter and full year 2024 financial results on Wednesday, February 26, 2025, at 4:30 p.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 February 26, 2025 FoRx Therapeutics AG, a Swiss-based company committed to discovering and developing innovative drugs targeting cancer-relevant DDR (DNA Damage Response) pathways, reported that it has appointed Jens Würthner, MD PhD, as Chief Medical Officer (Press release, FoRx Therapeutics, FEB 26, 2025, View Source [SID1234650656]). He is further strengthening FoRx Therapeutics’ existing management team with CEO Tarig Bashir, CSO Frank Zenke, and Head of Chemistry Ulrich Lücking.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jens Würthner has 20+ years of clinical development expertise and a track record that includes the successful progression of drug candidates from Phase I initiation to market approval. He has led clinical development programs at large pharmaceutical companies, namely Novartis, GlaxoSmithKline and AstraZeneca, as well as at biotech companies, such as ADC Therapeutics. At Swiss-based ADC Therapeutics, Jens oversaw all aspects of clinical development of several successful programs, including loncastuximab teserine (Zynlonta). Before that, he was Lead Clinical Program Leader at Novartis, where he was responsible for progressing small molecule compounds and a monoclonal antibody into the clinic and through multiple clinical trials. Jens joins FoRx Therapeutics from the Dutch company Scenic Biotech, where he has been building the translational and clinical teams for the oncology and rare disease franchise in preparation for first-in-human studies.

Jens Würthner holds an MD and a PhD from the University of Hamburg and completed a postdoctoral fellowship at the Laboratory of Cell Regulation & Carcinogenesis, National Cancer Institute, National Institutes of Health in Bethesda, Maryland (USA).

Tarig Bashir, PhD, CEO of FoRx Therapeutics, commented: "We are very happy that Jens is now part of our team. His long-standing expertise and track record in the clinical development of oncology therapeutics across all development stages is an outstanding asset for building FoRx Therapeutics’ clinical capabilities and will be key to successfully advancing our PARG inhibitor FORX-428 with its best-in-class profile through the clinic. We are excited to have Jens on board to work on our common and ambitious goal to improve patients’ lives and ultimately cure cancer."

Jens Würthner, MD PhD, CMO added: "I am looking forward to this new challenge at FoRx Therapeutics. Together with the team and all stakeholders, we will advance the Company’s lead development candidate FORX-428 with its convincing best-in-class profile into the clinic and through subsequent clinical studies. We are committed to bringing a novel therapeutic with transformative potential to cancer patients who have limited therapy options and require new targeted treatment approaches."

Pipeline update

Also today, the Company provided an update on its lead development candidate, FORX-428. The compound is an inhibitor of PARG (Poly(ADP-ribose) glycohydrolase) and is being developed for the treatment of solid tumors. FoRx Therapeutics reports significant progress towards IND (Investigational New Drug) submission for FORX-428 and anticipates clearance from the FDA by mid-2025. The Company has successfully finalized toxicological testing conducted according to GLP (Good Laboratory Practice) and also reports the identification and preclinical validation of predictive biomarkers which will be key in selecting patient populations most likely to benefit from treatment with FORX-428. Furthermore, recent data from animal studies with cell line-derived and patient-derived tumor models demonstrate outstanding anti-tumor efficacy and good tolerability, further corroborating the best-in-class proposition for FORX-428.

FoRx Therapeutics holds all development and commercial rights to FORX-428.

On February 26, 2025 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, reported its results for the quarter and year ended December 31, 2024 (Press release, Corcept Therapeutics, FEB 26, 2025, https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-announces-fourth-quarter-and-full-year-2024 [SID1234650625]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Financial Results

"Once again, we had a record number of new Korlym prescribers and a record number of patients receiving Korlym in the quarter. Physicians are increasingly aware of hypercortisolism’s true prevalence and the poor health outcomes for patients who go untreated. Screening is becoming more common and the number of patients receiving appropriate care continues to increase. We are confident that our Cushing’s syndrome business will grow for many years," said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer.

Corcept’s fourth quarter 2024 revenue was $181.9 million, compared to $135.4 million in the fourth quarter of 2023. Revenue for the full year was $675.0 million, compared to $482.4 million in 2023.

Net income was $30.7 million in the fourth quarter, or $0.26 diluted net income per common share, compared to net income of $31.4 million, or $0.28 diluted net income per common share, in the fourth quarter of 2023. Net income was $141.2 million for the full year, or $1.23 diluted net income per common share, compared to net income of $106.1 million, or $0.94 diluted net income per common share, in 2023.

Cash and investments were $603.2 million at December 31, 2024 compared to $425.4 million at December 31, 2023. In 2024, Corcept paid $38.0 million to purchase its common stock pursuant to the company’s stock repurchase program, net exercise of employee stock options and net vesting of restricted stock grants.

Clinical Development

"We made substantial progress in all of our clinical development programs in 2024," added Dr. Belanoff. "We submitted a New Drug Application (NDA) for our proprietary, selective cortisol modulator, relacorilant, as a treatment for hypercortisolism, based on compelling results from our GRACE, GRADIENT, long-term extension and Phase 2 studies. Our CATALYST study demonstrated that hypercortisolism is much more common than previously assumed in patients with difficult-to-control diabetes and that treatment with a cortisol modulator can significantly improve their glucose control. We expect data from ROSELLA, our pivotal study in women with platinum-resistant ovarian cancer, this quarter."

Hypercortisolism (Cushing’s Syndrome)

Relacorilant for patients with hypercortisolism – NDA submitted in December 2024
GRACE – Pivotal Phase 3 trial of relacorilant in 152 patients with all etiologies of hypercortisolism – primary endpoint achieved in randomized withdrawal phase; open-label phase demonstrated clinically meaningful improvements in a broad range of hypercortisolism signs and symptoms; relacorilant was well-tolerated, consistent with its known safety profile, with no cases of endometrial hypertrophy or drug-induced vaginal bleeding, relacorilant-induced hypokalemia, adrenal insufficiency or QT prolongation
GRADIENT – Supportive data for NDA – Patients treated with relacorilant exhibited clinically meaningful improvements in a broad range of hypercortisolism signs and symptoms in randomized, double-blind, placebo-controlled, Phase 3 trial in 137 patients with hypercortisolism caused by adrenal gland pathology; relacorilant was well-tolerated, consistent with its known safety profile, including no cases of endometrial hypertrophy or drug-induced vaginal bleeding, relacorilant-induced hypokalemia, adrenal insufficiency or QT prolongation
Phase 3 long-term extension study – Supportive data for NDA – clinically meaningful and durable cardiometabolic improvements exhibited in 116 patients who completed the GRACE, GRADIENT or Phase 2 relacorilant studies, with no new or notable safety signals observed; treatment duration of up to six years
CATALYST Part 1 – Of 1,057 patients with difficult-to-control type 2 diabetes, 23.8 percent were found to have hypercortisolism
CATALYST Part 2 – Primary endpoint met in randomized, double-blind, placebo-controlled study of 136 patients identified with hypercortisolism in CATALYST Part 1; patients who received Korlym exhibited a clinically meaningful and statistically significant improvement in hemoglobin A1c, with a decrease from baseline of 1.47 percent compared to a decrease of 0.15 percent in patients who received placebo (p-value: < 0.0001); safety profile of Korlym in this study was consistent with the medication’s label; no new adverse events were observed
MOMENTUM – 1,000-patient trial examining the prevalence of hypercortisolism in patients with resistant hypertension to begin this quarter
"The positive results from our pivotal GRACE study, and confirmatory evidence from our GRADIENT, long-term extension and Phase 2 studies, provide powerful support for relacorilant’s NDA in hypercortisolism. Patients in these studies experienced clinically significant improvements in a wide array of hypercortisolism’s signs and symptoms, without the off-target effects and toxicities that accompany currently available treatments. Relacorilant’s strong efficacy and safety profile positions it to become the new standard of care for patients with hypercortisolism," said Bill Guyer, PharmD, Corcept’s Chief Development Officer.

"CATALYST is a landmark study that will change the way physicians treat some of their sickest patients. Its findings are striking: One-in-four patients whose type 2 diabetes resists treatment with the best available medications have hypercortisolism and hyperglycemia in these patients responds powerfully to treatment with a cortisol modulator," added Dr. Guyer. "We plan to build on these findings. Our MOMENTUM study will establish the prevalence of hypercortisolism in patients with resistant hypertension."

Oncology

ROSELLA – Results expected this quarter from pivotal Phase 3 trial of relacorilant plus nab-paclitaxel in 381 patients with platinum-resistant ovarian cancer
Early-stage prostate cancer – Enrollment continues in randomized, placebo-controlled, Phase 2 trial of relacorilant plus enzalutamide in patients with early-stage prostate cancer, conducted in collaboration with the University of Chicago
"If ROSELLA replicates the positive results of our large, controlled, Phase 2 study, it will constitute a major medical advance and serve as the basis for relacorilant’s next NDA. We expect progression-free survival results this quarter," said Dr. Guyer. "Relacorilant has the potential to become the standard of care for patients with platinum-resistant ovarian cancer."

Amyotrophic Lateral Sclerosis (ALS)

DAZALS – In a randomized, double-blind, placebo-controlled Phase 2 study in 249 patients with ALS, dazucorilant did not meet its primary endpoint of improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R); a statistically significant improvement in overall survival at week 24 was observed; an open-label, long-term extension study is ongoing and one-year overall survival results are expected in the second quarter
"ALS is a devastating disease, with few good treatment options. In DAZALS, patients who received dazucorilant did not show improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R), which was the study’s primary endpoint. An improvement in overall survival was observed at week 24 of the study – no deaths (0 of 83 patients) were observed in the 300 mg dazucorilant arm, compared to 5 deaths (5 of 82 patients) in the placebo group (p-value: 0.02). The open-label, long-term extension study is ongoing and we expect one-year overall survival results in the second quarter," said Dr. Guyer.

Metabolic Dysfunction-Associated Steatohepatitis (MASH)

MONARCH – Enrollment continues in randomized, double-blind, placebo-controlled, Phase 2b trial of miricorilant in 120 patients with biopsy-confirmed MASH and in 75 patients with presumed MASH
"In our Phase 1b study, miricorilant reduced liver fat very rapidly, improved liver health and key metabolic and lipid measures and was well-tolerated. We look forward to building on these promising results in our MONARCH study," said Dr. Guyer.

Conference Call

We will hold a conference call on February 26, 2025, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time). Participants must register in advance of the conference call by clicking here. Upon registering, each participant will receive a dial-in number and a unique access PIN. Each access PIN will accommodate one caller. A listen-only webcast will be available by clicking here. A replay of the call will be available on the Investors / Events tab of Corcept.com.

On February 26, 2025 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported the presentation of a compilation of data at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) IO Conference (Press release, Sonnet BioTherapeutics, FEB 26, 2025, View Source [SID1234650641]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As part of the conference, Dr. Sant Chawla, Principal Investigator at the Sarcoma Oncology Center in Santa Monica, California, presented a poster entitled, "Combination immunotherapy with an albumin-binding interleukin-12 fusion protein that extends cytokine half-life, targets the tumor microenvironment, and enhances therapeutic efficacy." This is the first time the overall strategy of Sonnet’s Fully Human Albumin Binding (FHAB) platform has been compiled with existing data and presented in a poster. The presented poster is now available on the Publications page of the Company’s website.

SON-1010 is the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12), configured using genetic fusion to the FHAB platform, which extends the half-life and bioactivity of the IL-12 component due to binding native albumin in the serum. Albumin binding to FcRn, GP60, and SPARC results in an improved PK profile, decreased toxicity risk, and a broader therapeutic index preclinically, with significant targeting of the tumor microenvironment and increases in activated NK, NKT, Th1, and cytotoxic CD8 T cells, as well as marked repolarization of pro-tumor M2 MDSCs to inflammatory M1 APCs.

"Recombinant interleukins have generally had limited clinical success due to inefficient tumor targeting, short half-lives, and off-target toxicity. As previously disclosed, our novel FHAB platform has demonstrated the potential for us to design product candidates that safely extend the half-life of cytokines and deliver them to the tumor, where they can convert the immunological response from ‘cold’ to ‘hot’ and potentially realize the promise of immunotherapy. We are pleased to share the compilation of data in this poster presentation and look forward to announcing additional data from our ongoing studies evaluating our SON-1010 platform in 2025," commented Pankaj Mohan, Ph.D., Founder and Chief Executive Officer of Sonnet.

Key Highlights:

● A platform strategy was developed that links cytokines to the FHAB as mono- or bifunctional fusions to bind native albumin at both physiologic and acidic pH, taking advantage of albumin’s long serum half-life and concentration in tumors, allowing delivery to and accumulation of the drug in the TME. IL-12 is a potent cytokine that stimulates the innate and adaptive immune responses, functioning in combination with other cytokines, like IL-15 and IL-18. Several approaches are currently being studied in humans, such as:

○ SON-1010 monotherapy at the highest dose is continuing in patients with advanced solid tumors. In December 2024, the Company disclosed clinical benefit in 48% of patients, including a partial response at the highest dose in a patient with clear cell sarcoma. The poster reflects the current status of this trial.

○ Co-administration with a checkpoint inhibitor (atezolizumab) to activate local immune cells and upregulate PD-L1 in the TME. Safety has been monitored at each dose escalation step and the most common adverse events at each dose level have been updated for the results currently available.

○ SON-1010 is being administered alternating with an immunoreactive chemotherapy drug (trabectedin) to enhance its ability to activate a pro-inflammatory phenotype in the TME.

○ Alternating administration with a potent chemotherapeutic regimen (NALIRIFOX) will be done in front-line patients with pancreatic ductal adenocarcinoma (PDAC) to enhance their response.

● Each setting has the potential to augment the effects of the licensed therapy in populations that continue to have high unmet needs for an improved outcome. Immunotherapy allows greater flexibility in selecting potentially synergistic combinations for rational implementation.

● SON-1010 and SON-1210 address paramount safety and tolerability factors, which have traditionally hindered the use of therapeutic cytokines in the treatment of solid tumors, by extending the cytokine half-life and improving the therapeutic index that may result in better patient outcomes.

SON-1010 is being evaluated in a Phase 1b/2a dose-escalation and proof-of-concept study (SB221) in combination with SON-1010 and atezolizumab (Tecentriq) (in collaboration with Genentech, a member of the Roche Group), which is focused on platinum-resistant ovarian cancer (PROC) (NCT05756907). The extended PK of SON-1010, along with its ability to induce IFNγ in the TME causing upregulation of PD-L1, creates an opportunity for synergistic activity. Enrollment remains ongoing and an update on safety at the MTD in that trial is expected in Q1 calendar year 2025. Another trial evaluating dose escalation of SON-1210 (IL12-FHAB-IL15), followed by its combination with NALIRIFOX in patients with metastatic pancreatic cancer, is expected to begin later this calendar year.

About SON-1010

SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This single-chain antibody fragment was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be linked using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), several types of cancer, such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant to this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

On February 26, 2025 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA," the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported the trial design for the expansion of its THIO-101 pivotal Phase 2 trial in non-small cell lung cancer (NSCLC) (Press release, MAIA Biotechnology, FEB 26, 2025, View Source [SID1234650657]). Following successful outcomes to date in THIO-101, the expansion of the study will assess overall response rates (ORR) in advanced NSCLC patients receiving third line (3L) therapy who were resistant to previous checkpoint inhibitor treatments (CPI) and chemotherapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The THIO-101 study in 3L will enroll up to 48 patients with two arms: Arm 1, continuing the evaluation of THIO sequenced with Libtayo (cemiplimab); and Arm 2, evaluating THIO as a monotherapy, to further gain experience of THIO in the contribution of components. Treatment cycles for patients in both arms will administer THIO on 3 consecutive days, followed by immune activation on day 4. Arm 1 will administer Libtayo on day 5. The Company plans to enroll an additional 100 patients for the registration phase of the trial. MAIA expects to conduct the trials in the U.S. and select countries in Europe and Asia.

MAIA recently announced an amended clinical supply agreement with Regeneron to include the expansion portion of THIO-101. Under terms of the amended agreement, MAIA continues to sponsor THIO-101 and Regeneron will provide Libtayo for the treatment of all patients including the additional patients in the expansion and potentially, the registration studies.

"We are excited to start the expansion arm of our THIO-101 trial which is designed to determine overall response rates in third line NSCLC. We expect to have new patients enrolled in the coming weeks," said Vlad Vitoc, M.D., CEO of MAIA. "Through THIO-101 to date, THIO has delivered unprecedented disease control, response, and survival results. Continued efficacy and safety data generated by our study could support an FDA NDA submission directly, particularly as we plan to seek an accelerated approval of THIO in the U.S.

"We have multiple milestones that we believe are attainable for 2025 and we look forward to keeping our shareholders and investors well informed of our progress on value creation," Dr. Vitoc added.

As of January 15, 2025, data indicated that Median Overall Survival (OS) in third-line treatment was reached at 16.9 months, with a 95% confidence interval (CI) lower bound of 12.5 months and a 99% CI lower bound of 10.8 months). The treatment has been generally well-tolerated to date in this heavily pre-treated population1.

Details on safety can be found on the previously announced SITC (Free SITC Whitepaper) 2024 presentation available on MAIA’s website.

About THIO
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, a Phase 2 Clinical Trial
THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. Treatment with THIO followed by cemiplimab (Libtayo) has been generally well-tolerated to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.