On August 26, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) has approved Ordspono (odronextamab) to treat adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. This marks the first regulatory approval of Ordspono in the world for these patients (Press release, Regeneron, AUG 26, 2024, View Source [SID1234646101]). Ordspono is a bispecific antibody that acts by linking the lymphoma cell to a killer T cell.

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"The EC approval of Ordspono is a meaningful advancement for EU patients and their physicians as a new option to treat both indolent and aggressive lymphomas," said Stefano Luminari, M.D., Professor of Oncology at the University of Modena and Reggio Emilia, hematologist at the Hematology Unit of Arcispedale Santa Maria Nuova in Reggio Emilia, and a trial investigator. "In clinical trials, Ordspono demonstrated remarkable complete response rates in follicular lymphoma, as well as compelling efficacy results in diffuse large B-cell lymphoma, including in the post-CAR-T setting. Physicians, especially in the community setting, will have an off-the-shelf option that can be administered out-patient – offering the chance for complete remission."

The approval is based on results from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 trials, which demonstrated robust, durable response rates in adults with R/R FL or R/R DLBCL:

In R/R FL, results from ELM-2 (N=128) as assessed by an independent review committee (IRC) showed an objective response rate (ORR) of 80%, with 73% achieving a complete response (CR). Among complete responders, the median duration of response (DoR) was 25 months (95% confidence interval [CI]: 20 months to not estimable [NE]).
In R/R DLBCL,
results from ELM-2 (N=127) in patients who were CAR-T therapy naive, as assessed by an IRC showed 52% ORR, with 31% achieving a CR. Among complete responders the median DoR was 18 months (95% CI: 10 months to NE).
results from ELM-1 (N=60) in patients who had progressed after CAR-T therapy, as assessed by an IRC showed 48% ORR, with 32% achieving a CR. Among responders (n=29), the median DoR was 15 months (95% CI: 3 months to NE).
The most common adverse reactions were cytokine release syndrome (CRS; 54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), diarrhea (24%) and COVID-19 (22%). The most common serious adverse reactions were CRS (14%), pneumonia (9%), COVID-19 (9%) and pyrexia (6%). Ordspono can cause serious or fatal infections, and CRS, which may be serious or life-threatening.

"Ordspono marks the first approval from our bispecific antibody platform, which we hope will increasingly contribute to our growing portfolio of practice-changing medicines for oncology and other diseases," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "Building upon this approval, we are excited about our OLYMPIA program, which includes multiple Phase 3 trials investigating Ordspono as a monotherapy and in various combinations, in earlier lines of therapy. We’re also excited to be advancing our broader pipeline of CD3 and other bispecific therapies, both to additional hematologic cancers such as myeloma, as well as to solid tumors."

About FL and DLBCL
FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). While FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment. It is estimated that approximately 120,000 FL cases and 163,000 DLBCL cases are diagnosed annually worldwide. In Europe, it is estimated that approximately 15,000 FL cases and 31,000 DLBCL cases are diagnosed each year.

About the Ordspono (odronextamab) Clinical Trial Program
Ordspono is a CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing. Ordspono as monotherapy is indicated for the treatment of adult patients with R/R FL or R/R DLBCL, after two or more lines of systemic therapy. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu in due course.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is ORR according to the Lugano Classification as assessed by IRC, and secondary endpoints include CR, progression-free survival, overall survival and DoR.

Regeneron is conducting a broad Phase 3 development program, known as OLYMPIA, investigating odronextamab in earlier lines of therapy and other B-NHLs. In addition, Regeneron is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and Regeneron’s PD-1 inhibitor cemiplimab for R/R aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. For more information, visit the Regeneron clinical trials website, or contact via [email protected] or +1 844-734-6643.

About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.

On August 26, 2024 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to opaganib for treatment of neuroblastoma, a type of childhood cancer that develops from immature nerve cells and accounts for 15% of all pediatric cancer-related deaths (Press release, RedHill Biopharma, AUG 26, 2024, View Source [SID1234646100]).

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Orphan Drug designation provides for a seven-year marketing exclusivity period should opaganib be approved in neuroblastoma and may confer additional benefits such as accelerated development and review times, potential grant funding and possible tax credits.

"RedHill is proud to have received a second orphan-drug designation for opaganib in oncology, following its previous designation for cholangiocarcinoma (CCA, also known as bile duct cancer). This designation for neuroblastoma – the most common infancy malignancy and for which new options are urgently needed – adds to opaganib’s potential as a novel oncological agent," said Dr. Mark Levitt, Chief Scientific Officer at RedHill. "Opaganib has broad oncology potential with promising preliminary clinical data in solid tumor cancers such as prostate cancer and CCA, and data from a range of U.S. government supported and Apogee conducted preclinical studies in various indications, including radioprotection, and also in combination with RedHill’s RHB-107. We also see such utility extending to the potential for opaganib to have a sensitizing effect in hormone receptor pathway inhibition therapy, which the Company expects to test in a planned externally funded Phase 2 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to opaganib for treatment of neuroblastoma, a type of childhood cancer that develops from immature nerve cells and accounts for 15% of all pediatric cancer-related deaths.

Orphan Drug designation provides for a seven-year marketing exclusivity period should opaganib be approved in neuroblastoma and may confer additional benefits such as accelerated development and review times, potential grant funding and possible tax credits.

"RedHill is proud to have received a second orphan-drug designation for opaganib in oncology, following its previous designation for cholangiocarcinoma (CCA, also known as bile duct cancer). This designation for neuroblastoma – the most common infancy malignancy and for which new options are urgently needed – adds to opaganib’s potential as a novel oncological agent," said Dr. Mark Levitt, Chief Scientific Officer at RedHill. "Opaganib has broad oncology potential with promising preliminary clinical data in solid tumor cancers such as prostate cancer and CCA, and data from a range of U.S. government supported and Apogee conducted preclinical studies in various indications, including radioprotection, and also in combination with RedHill’s RHB-107. We also see such utility extending to the potential for opaganib to have a sensitizing effect in hormone receptor pathway inhibition therapy, which the Company expects to test in a planned externally funded Phase 2 study."

Neuroblastoma usually affects children aged five or younger but does also occur in older children. In the United States, approximately 650 new cases are diagnosed each year, accounting for around 10% of all childhood cancer cases. Treatment typically involves a combination of surgery, chemotherapy, radiation therapy, and sometimes targeted therapy or immunotherapy. New options are urgently needed.

The neuroblastoma market is expected to reach almost $1.5 billion before the middle of the next decade.

Opaganib is in development for multiple oncology, viral, inflammatory and diabetes and obesity-related indications, including COVID-19, Ebola, acute respiratory distress syndrome (ARDS) and radio/chemical protection.

About Neuroblastoma
Neuroblastoma is a type of cancer most commonly affecting babies and young children. It is rare but is the most common infancy malignancy with a median age of diagnosis of 17 months. In the U.S. it accounts for up to around 10% of all childhood cancer cases. It affects around 11 to 13 kids per million children aged younger than 15 years old – with incidence rising to 65 per million in babies under one year old, equating to approximately 650 new cases each year.

Neuroblastoma originates from nerve cells called neuroblasts, which are found in the adrenal glands (located above the kidneys) and in nerve tissue along the spine, chest, abdomen, or pelvis. The exact cause of neuroblastoma is not well understood, but genetic mutations and abnormalities are known to play a role. Some cases may be linked to genetic syndromes or family history, although most occur sporadically without a clear inherited pattern.

The outlook for children with neuroblastoma can vary widely. Factors affecting prognosis include the stage of the disease at diagnosis, the age of the child, and specific biological characteristics of the tumor. Neuroblastoma is known for its ability to sometimes regress spontaneously in very young children, but it can also be aggressive and challenging to treat, accounting for 15% of pediatric cancer-related deaths.

About Opaganib (ABC294640)
Opaganib, a proprietary investigational host-directed and potentially broad-acting drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including obesity-related syndromes, prostate cancer and cholangiocarcinoma (bile duct cancer), gastrointestinal acute radiation syndrome (GI-ARS), Sulfur Mustard exposure, COVID-19, Ebola and other viruses as part of pandemic preparedness.

Opaganib’s host-directed action is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).

Opaganib has been selected for evaluation by two U.S. government countermeasures programs for Acute Radiation Syndrome (ARS) and Sulfur Mustard exposure, both funded by the NIH: The Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the HHS National Institutes of Health, for the nuclear medical countermeasures (MCM) product development pipeline selected opaganib for development as a potential treatment for Acute Radiation Syndrome (ARS); and the Chemical Medical Countermeasures (Chem MCM) Program and the Chemical Countermeasures Research Program (CCRP), managed respectively by the Administration for Strategic Preparedness and Response (ASPR) / Biomedical Advanced Research and Development Authority (BARDA) and NIH/NIAID selected opaganib for evaluation as a potential medical countermeasure (MCM) against Sulfur Mustard exposure.

Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A and Ebola. Opaganib delivered a statistically significant increase in survival time when given at 150 mg/kg twice a day (BID) in a United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, making it the first host-directed molecule to show activity in Ebola virus disease. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury, Gilead Sciences Inc.), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study.

Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in medRxiv.

Opaganib has received Orphan Drug designation from the FDA for the treatment of neuroblastoma and cholangiocarcinoma and has undergone studies in advanced cholangiocarcinoma (Phase 2a) and prostate cancer. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.

Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications.

On August 26, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in the following investor conferences in September (Press release, ORIC Pharmaceuticals, AUG 26, 2024, View Source [SID1234646099]):

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2024 Wells Fargo Healthcare Conference – Participating in a fireside chat on Thursday, September 5, 2024, at 8:00 a.m. ET
Baird 2024 Global Healthcare Conference (Available to conference attendees only) – Participating in a fireside chat on Tuesday, September 10, 2024, at 10:50 a.m. ET.
2024 Cantor Global Healthcare Conference – Participating in a fireside chat on Thursday, September 19, 2024, at 8:35 a.m. ET
Live webcasts of the Wells Fargo and Cantor discussions will be available through the investor section of the company’s website at www.oricpharma.com. Replays of the webcasts will be available for 90 days following the events.

On August 26, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable", "Notable Labs" or the "Company"), a clinical-stage precision oncology company developing new cancer therapies identified by its Predictive Medicine Platform (PMP), reported that Thomas A. Bock, MD has resigned from his positions as Chief Executive Officer (CEO) and member of the Board of Directors of the Company, effective today (Press release, Notable Labs, AUG 26, 2024, View Source [SID1234646097]).

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Joseph Wagner, PhD, the Company’s Chief Scientific Officer (CSO), has been appointed as interim CEO. The Board of Directors has initiated a search process for Dr. Bock’s successor.

"On behalf of the Board and the entire Notable team, I want to extend our deepest gratitude to Thomas for his visionary leadership and tireless dedication to the Company. Under his leadership, Notable transformed from a private diagnostic start-up to a publicly-traded clinical-stage therapeutic-focused leader in Predictive Medicine and delivered industry-leading results from platform-validating clinical trials in hematologic cancers. We are confident that the strong foundation Thomas built will lead to continued progress, starting with the initiation of the Phase 2 clinical program for volasertib, expected in the coming months," said Tuomo Pätsi, Chairman of the Board. "As we search for Thomas’ successor, we look forward to working with Joe to continue Notable’s work to revolutionize the use of predictive medicine in cancer care."

"I am especially proud of Notable’s world-class team and how far the Company has come in developing PMP as a novel precision medicine tool. I believe the re-designed volasertib development program, which merges biology and technology through enhanced trial design and the use of PMP, has the potential to improve treatment outcomes for patients with AML," said Dr. Bock. "With our FDA-cleared Phase 2 program nearing significant clinical milestones, I am optimistic for Notable’s future and thankful to our team, Board, investors, advisors, and all partners for their shared commitment and the sense of urgency that patients deserve."

Dr. Bock will continue as a consultant to the Company, advising the Board of Directors and offering his expertise and guidance on the Company’s next phase.

About Volasertib

Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize its PMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted Breakthrough Therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers.

On August 26, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported corporate highlights and unaudited financial results for the first half-year of 2024.

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"In the first half of 2024, we made substantial progress with our Radio-DARPin Therapy (RDT) platform. We nominated the first RDT candidate, MP0712 targeting DLL3, and we look forward to bringing it to patients in 2025 with our partner Orano Med, the leader in the 212Pb field. With them, we entered into a strategic collaboration earlier this year, to access and leverage their supply and manufacturing capabilities, as well as clinical experience, with radiopharmaceuticals, to co-develop Radio-DARPin Therapeutics together," said Patrick Amstutz, Ph.D., Molecular Partners’ Chief Executive Officer. "Additionally, we progressed our immune cell engagers, including the cKit Switch-DARPin MP0621 into pre-clinical studies, and progressed MP0533 in AML to the top planned dose, seeing initial clinical responses and now testing dose intensification."

Research & Development Highlights

Radio-DARPin Therapy (RDT) Platform and MP0712
Molecular Partners has leveraged the intrinsic properties of DARPins, such as small size, high affinity and specificity, to engineer Radio-DARPins as ideal vector candidates for radiopharmaceutical therapeutics and to create a Radio-DARPin Therapy (RDT) platform amenable to a broad range of tumor targets. Historically, small protein-based vectors faced challenges with kidney accumulation and toxicity, as well as suboptimal tumor uptake. Molecular Partners’ RDT platform addresses these limitations with its half-life extension technologies and surface engineering approaches, while preserving the advantages of the small protein format.

Throughout H1 2024, Molecular Partners has continued to demonstrate the RDT platform’s ability to deliver on its intended design. The Company has engaged with scientific experts in radiopharmaceutical innovation, as well as investor and clinical communities to build awareness of the unique offering of Radio-DARPins and to identify opportunities for potential RDT portfolio growth.

In January 2024, Molecular Partners entered into a strategic collaboration with Orano Med to co-develop 212Pb-based RDTs for patients with solid tumors. The partnership combines Molecular Partners’ leadership in DARPins, as a highly differentiated modality for tumor-targeted delivery of radioisotopes, with Orano Med’s leading expertise and capabilities in Targeted Alpha Therapy to further advance the RDT platform and expand Molecular Partners’ RDT portfolio. 212Pb represents the next generation of targeted alpha therapies, with a selective, safe, and potent profile in patients: in addition to virtually endless supply of starting material, Orano Med has established robust and independent supply and manufacturing capabilities required for seamless delivery of targeted alpha therapies to clinical sites.

In June 2024, Molecular Partners nominated MP0712 as its first RDT candidate, a 212Pb-based DLL3-targeting RDT in its co-development program with Orano Med. The supporting preclinical data were presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 Annual Meeting which took place in Toronto, Canada.

DLL3 is a priority target for radiopharmaceutical therapy based on its abundant expression in over 85% small cell lung cancer (SCLC) patients and other aggressive neuroendocrine tumors, while its expression in healthy tissues is low. SCLC is an aggressive form of lung cancer, with a poor five-year survival prognosis and a high unmet need for patients.

The data presented at SNMMI provide strong support for the clinical development of MP0712 in SCLC and other DLL3-expressing neuroendocrine tumors. In vivo data demonstrated strong and homogeneous tumor uptake, as well as substantial and durable inhibition of tumor growth at clinically relevant doses. Furthermore, the in vivo data suggested a favorable preclinical safety profile and support MP0712’s potential for clinical use. Achieving favorable tumor to kidney ratios and biodistribution are key design objectives for this program. In both areas MP0712 performed well in mouse xenograft tumor models; tumor to kidney ratios over two were observed, and close to 60% of the injected dose per gram of tissue was detectable in the tumor.

The replicable learnings from the development and optimization of MP0712, as well as additional RDT platform improvements, are being taken forward to the broader RDT portfolio. Molecular Partners will present additional data in an oral presentation at the 2024 Congress of the European Association of Nuclear Medicine (EANM) in October 2024, and plans to initiate a first-in-human clinical trial of MP0712 in 2025.

In addition to the above updates, Molecular Partners continued to progress its RDT portfolio of projects in partnership with Novartis and is evaluating additional targets for RDT programs.

MP0533
MP0533, a novel tetra-specific T cell-engaging DARPin, is currently being evaluated in a Phase 1/2a clinical trial for patients with relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome/AML (MDS/AML) (ClinicalTrials.gov: NCT05673057). The mechanism of action of MP0533 is designed to preferentially kill AML cells (blasts, leukemic progenitor and stem cells) that express any combination of the three cell surface antigens CD33, CD123, and CD70, while sparing healthy cells, which tend to express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T cell-engagement.

In April 2024, comprehensive preclinical data supporting MP0533’s proposed unique mechanism of action for the treatment of AML was published in Cancer Immunology Research (View Source), a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

In the ongoing Phase 1/2a clinical trial, as of 29 July 2024, MP0533 has demonstrated an acceptable safety profile with the majority of adverse events reported being infusion-related reactions and cytokine release syndrome. Four clinical responses have been observed among the 28 patients across dosing regimens (DR) 1–6. These included a complete response in DR 4 and a morphologic leukemia-free state in three patients, one each in DRs 3, 5 and 6. Furthermore, an encouraging trend in bone marrow blast cell reductions was observed as of the data cut-off date; 7 of 26 evaluable patients and 5 of 11 patients with low disease burden at baseline (blasts <20%) displayed a blast reduction over 50%.

At present, data are being collected for DR7 and dose escalation continues with DR 8 open. Based on the observed safety profile and encouraging initial antitumor activity data, and following discussion with treating physicians and key opinion leaders, Molecular Partners is amending the protocol to further increase dosing and improve the exposure profile of MP0533. The Company’s aim is to achieve higher response rates, as well as improved depth and duration of responses in r/r AML patients. Molecular Partners plans to present a clinical update on the program in H2 2024, and on the amended dosing scheme for MP0533 in 2025.

Switch-DARPin Platform and first candidate MP0621
The Switch-DARPin platform represents a novel innovative DARPin-based approach by Molecular Partners that provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates, allowing target activation only in the presence of a defined set of antigens. The goal is conditional activation of a targeted immune response. The first Switch-DARPin program, MP0621 (cKit x CD16a x CD47), was introduced in January 2024 and is designed to induce killing of hematopoietic stem cells as a next-generation conditioning regimen. Molecular Partners’ intends to extend access to potentially curative HSCT for more patients with AML as well as those with other hematologic malignancies or genetic diseases requiring HSCT.

In June 2024, the Company presented preclinical proof-of-concept data from MP0621 at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress which took place in Madrid, Spain. The safety, efficacy and pharmacokinetic data supported MP0621’s ability to selectively kill cKit positive cells and conditionally block the immunosuppressive protein CD47, with limited systemic side effects.

Crucially, these preclinical data also validated the Switch-DARPin concept, demonstrating that a logic-gated immune activation with a reversible switch can be achieved with a DARPin design. This provides another novel DARPin approach for conditional activation of anticancer immunotherapies and its utilization to locally engage immune-modulating targets not amenable to other treatment modalities. Further preclinical studies are ongoing with updates for the MP0621 program planned for H2 2024.

MP0317
MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts around tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

In June 2024, the Company presented positive data from its completed Phase 1 dose-escalation clinical trial of MP0317 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024 which took place in Chicago, IL, USA.

The final analysis included 46 patients with advanced solid tumors and confirmed earlier reported interim results. MP0317 displayed a favorable and manageable safety profile across all nine planned dosing cohorts (0.03–10 mg/kg) administered intravenously weekly or every 3 weeks with only one patient experiencing a dose-limiting toxicity (transient asymptomatic grade 3 elevation of liver enzymes). The most frequently observed adverse reactions were fatigue and lower grade infusion-related reactions (grade 1–2). MP0317 treatment resulted in target occupancy in tumor biopsies with evidence of TME remodeling. In terms of clinical response, one patient achieved an unconfirmed partial response and stable disease was observed in 14 additional patients.

The positive data support further clinical evaluation of MP0317 in combination with complementary anticancer therapies and demonstrated the ability of the DARPin design to deliver on a targeted, tumor-localized CD40 activation mechanism. Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated combination trials.

Corporate and Management Highlights

On August 26 2024, Philippe Legenne, M.D., MBA, MHS, acting CMO and SVP Medical Strategy and Development, was appointed Chief Medical Officer at MP. "I am grateful that Phillippe is stepping fully into the role of CMO. Under his leadership, our MP0533 program has enrolled all dose cohorts at maximum speed, strongly supported by our investigators. This was only possible by the stellar performance by Philippe’s team. With his broad oncology background, ability to build a strong team and gift to engage trustfully with KOLs, he is in an ideal position to progress our first Radio-DARPin therapies towards clinical development in the months to come." said Patrick Amstutz, CEO of Molecular Partners.

Dr. Legenne joined Molecular Partners in early 2020. Over this time, he has led the clinical development strategy and execution across the Molecular Partners portfolio, including the successful initiation and seamless execution of MP0533, MP0317 and Ensovibep. Prior to joining Molecular Partners, Philippe held positions of increasing responsibility at JNJ, GSK, and Novartis, both in the United States and Europe. In his most recent role prior to Molecular Partners, Philippe led the EU medical organization for the oncology portfolio at Amgen. He received his medical degree from the Université de Lille (France), an MBA from ESSEC Business School (Paris) and a Master’s degree in health economics from Université Paris Dauphine-PSL.

As previously communicated, a putative class action complaint filed in July 2022 in the U.S. District Court for the Southern District of New York was dismissed without prejudice in the Company’s favor in February 2024 and was subsequently ordered closed.

At the Company’s Annual General Meeting on April 17, 2024, all motions proposed by the Board of Directors at the Annual General Meeting were approved by the shareholders of the Company.