On December 3, 2024 Keros Therapeutics, Inc. ("Keros" or the "Company") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta ("TGF-ß") family of proteins, reported an exclusive global development and commercialization license agreement with Takeda (TSE:4502/NYSE:TAK) to advance elritercept (Press release, Keros Therapeutics, DEC 3, 2024, View Source [SID1234648752]). Elritercept is currently in two ongoing Phase 2 clinical trials; one in patients with very low-, low-, or intermediate-risk myelodysplastic syndrome ("MDS") and one in patients with myelofibrosis ("MF"). The Phase 3 RENEW clinical trial evaluating elritercept in adult patients with transfusion-dependent anemia with very low-, low-, or intermediate-risk MDS will begin enrollment soon.

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Under the terms of the agreement, Takeda will obtain an exclusive license to further develop, manufacture and commercialize elritercept worldwide outside of mainland China, Hong Kong and Macau. Takeda will be responsible for all development, manufacturing and commercialization as of the effective date of the agreement. Subject to the terms of the agreement, Keros will receive a $200 million upfront cash payment and is eligible to receive development, approval and commercial milestones with the potential to exceed $1.1 billion. Keros will also be eligible to receive tiered royalties on net sales.

"We are thrilled to announce this agreement with Takeda, a leader in the hematologic oncology treatment space," said Jasbir S. Seehra, Ph.D., Chair and Chief Executive Officer of Keros. "We believe this global license further validates Keros’ position as a leader in understanding the role of the TGF-ß family of proteins and the broad potential of this biological pathway."

"We believe Takeda is an ideal partner to maximize the potential of elritercept’s differentiated profile and continue to build on the great progress our team has accomplished with elritercept," said Chris Rovaldi, President and Chief Operating Officer of Keros. "We expect that the net proceeds from the upfront payment will enable us to extend our operational runway into the fourth quarter of 2028, facilitating the continued advancement of cibotercept (KER-012) and KER-065, both of which are wholly-owned assets with near term clinical updates."

"We are excited to partner with Keros, an accomplished team with exceptional expertise in TGF-ß biology," said P.K. Morrow, Head of the Oncology Therapeutic Area Unit at Takeda. "Building on the promising results elritercept has shown in the clinic to date, we look forward to continuing to explore its potential and to having the opportunity to potentially deliver it to patients with hematologic disorders. This agreement aligns with our goal of advancing therapies that may shift the treatment paradigm for underserved patient populations."

The effectiveness of the agreement is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act ("HSR Act").

About Elritercept

Elritercept is an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-ß receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. Elritercept is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with MF.

On December 3, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it is in discussions and has an upcoming meeting with the U.S. Food and Drug Administration (FDA) regarding the evolving treatment landscape in endometrial cancer and any implications this may have with respect to the Company’s Phase 3 XPORT-EC-042 trial (Press release, Karyopharm, DEC 3, 2024, View Source [SID1234648751]). In light of this, Karyopharm does not plan to discuss its endometrial cancer program during the Piper Sandler 36th Annual Healthcare Conference being held in New York, NY today. The Company intends to provide an update on its endometrial cancer program as soon as practical following the discussion with FDA.

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A live webcast of the fireside chat at the Piper Sandler 36th Annual Healthcare Conference at 11:30 a.m. ET today can be accessed under "Events & Presentations" in the Investor section of the Company’s website, View Source, and will be available for replay following the event.

About the EC-042 Study
EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind study evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 study was initiated in November 2022 and is expected to enroll up to 220 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The primary endpoint of the study is progression free survival, as assessed by an investigator, with overall survival as a key secondary endpoint. Further, in connection with the EC-042 Study, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOneCDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type.

About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO/NEXPOVIO is marketed in these respective ex-U.S. territories by Karyopharm’s partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On December 3, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) and Biomunex Pharmaceuticals reported an exclusive global licensing agreement for BMX-502. BMX-502 is a bispecific antibody that engages and activates a subset of cytotoxic T cells called Mucosal-Associated Invariant T cells (MAIT cells) and targets the GPC3 tumor antigen, to kill cancer cells (Press release, Ipsen, DEC 3, 2024, View Source [SID1234648750]). GPC3 is a clinically validated target, highly expressed across several cancer types.1 MAIT cells are present throughout the body, highly enriched in many specific tissues of the body, particularly in mucosal and barrier tissues. BMX-502 offers a promising approach to treating tumors in these tissues.2,3

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Developed using Biomunex’s proprietary BiXAb technology, BMX-502 selectively engages MAIT cells and leverages their unique properties to maximize anti-tumor activity. MAIT engagers should overcome some of the limitations of current pan-T cell engager therapies, including activation of regulatory T cells and cytokine release syndrome, side effects that are difficult to manage for patients and represent a significant burden on the healthcare system.4 MAIT engagers have the potential to provide a more robust therapeutic window compared to classical pan-T cell engagers in specific tumor types.

"As we continue to grow Ipsen’s pipeline using a science-first approach to partnering across the ecosystem, we believe BMX-502 is a strong addition with first-in-class potential in solid tumors," said Mary Jane Hinrichs, SVP and Head of Early Development at Ipsen. "This new MAIT-engager program will complement our existing TCE portfolio as we harness the next-generation of T cell engagers to overcome treatment challenges, including dose-limiting toxicity, to bring transformational new medicines to people living with solid tumors around the world."

"This agreement with such an innovative oncology company as Ipsen is proof of the relevance of MAIT-engager approach of Biomunex, the first company worldwide to have identified the high therapeutic potential of MAIT cells in cancer treatment. It also represents the demonstration of the added-value of our best-in-class BiXAb platform to rapidly generate innovative and promising bispecific antibodies. We are convinced that our MAIT engagers will represent a new step forward in the development of disruptive immuno-therapies for the treatment of cancer. We look forward to initiating and supporting the development of BMX-502 alongside Ipsen," added Dr. Pierre-Emmanuel Gerard, founder, President and CEO of Biomunex.

Under the terms of the agreement, Biomunex will complete the IND-enabling package. Ipsen will assume responsibility for Phase I preparation activities, including submission of the Investigational New Drug (IND) application, and all subsequent clinical-development and global commercialization activities. Biomunex is eligible to receive up to $610 million, including upfront, contingent upon successful development, regulatory and commercial milestones, in addition to tiered global royalties on sales.

On December 3, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that abstracts related to lacutamab health-related quality of life and translational data from the TELLOMAK trial and SAR443579, Sanofi-partnered ANKET asset, have been selected for the American Society of hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Innate Pharma, DEC 3, 2024, View Source [SID1234648749]).

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"We are proud of the progress being made across our multiple programs, including our lead proprietary asset lacutamab and the multi-specific NK cell engagers from our ANKET platform," commented Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma. "We look forward to presenting data supporting the advancement of our programs at the upcoming ASH (Free ASH Whitepaper) 2024 as we move closer to our goal of delivering new treatment options for patients with high unmet medical needs."

Details of the presentations

•Lacutamab in Patients with Relapsed and/or Refractory Sézary Syndrome: Translational Analysis from the TELLOMAK Phase 2 Trial
Abstract Number: 1609
Presentation Type: Poster Presentation
Session: 622. Lymphomas: Translational – Non-Genetic: Poster I
Date and Time: Saturday, Dec. 7, 2024, 5:30 PM – 7:30 PM PT

•Health-Related Quality of Life in Patients with Relapsed/Refractory Cutaneous T-Cell Lymphoma Treated By Lacutamab: Patient-Reported Outcomes from the Phase 2 TELLOMAK Trial
Abstract: 466
Presentation Type: Oral Presentation
Session Name: 625. T Cell, NK Cell, or NK/T Cell Lymphomas: Clinical and Epidemiological: When Old Meets New in T Cell Lymphomas
Presentation Date and Time: Sunday, Dec. 8, 2024, 10:15 AM PT

•Phase 1/2, Open-Label, Multi-Center Study Assessing the Safety, Tolerability and Preliminary Efficacy of CD123 Natural Killer Cell Engager (NKCE), SAR443579, in Combination With Venetoclax and Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy (Sanofi)
Abstract: 2883.3
Presentation Type: Poster Presentation
Session Name: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster II
Date and Time: Sunday, Dec. 8, 2024, 6:00 PM – 8:00 PM PT

About Lacutamab

Lacutamab is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease, and peripheral T cell lymphoma (PTCL). Rare cutaneous lymphomas of T lymphocytes have a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

Lacutamab is granted European Medicines Agency (EMA) PRIME designation and US Food and Drug Administration (FDA) granted Fast Track designation for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. Lacutamab is granted orphan drug status in the European Union and in the United States for the treatment of CTCL.

On December 3, 2024 Epsilogen, the global leader in the development of immunoglobulin E (IgE) antibodies to treat cancer, reported that it has commenced a Phase Ib study evaluating MOv18 IgE in patients with platinum-resistant ovarian cancer (PROC) (Press release, Epsilogen, DEC 3, 2024, View Source [SID1234648748]).

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The Phase Ib, open-label, dose escalation and expansion trial (NCT06547840) will enrol 45 patients with PROC whose disease has progressed after no more than four lines of prior therapy. The trial will assess the safety, tolerability and efficacy of MOv18 IgE in ascending dose cohorts.

MOv18 IgE is an IgE antibody targeting the folate receptor alpha (FR alpha) antigen which is selectively expressed by a variety of cancers including ovarian, non-small cell lung, endometrial and triple negative breast cancer. It is the first ever IgE antibody therapeutic to enter clinical testing and the Phase Ib trial will generate extensive translational data to allow further understanding of IgE’s unique mechanism of action in man. A previous Phase I safety study of MOv18 IgE found it to be safe and well tolerated, with evidence of anti-tumour activity observed, as reported in Nature Communications (View Source).

Dr Tim Wilson, CEO of Epsilogen, said: "We are pleased to have initiated the Phase Ib study of MOv18 IgE, following the encouraging Phase I data. This is a key step in our goal of bringing this exciting new therapeutic modality to cancer patients".