On November 18, 2024 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company employing innovative technologies to develop best-in-class radiopharmaceuticals for cancer treatment and monitoring, reported to have entered into an exclusive worldwide license and collaboration agreement with Novartis Pharma AG, a subsidiary of Novartis AG (NYSE: NVS) (Press release, Ratio Therapeutics, NOV 18, 2024, View Source [SID1234648475]). The collaboration leverages Ratio’s radioligand therapy discovery and development expertise as well as its technology platforms for the development of a Somatostatin Receptor 2 (SSTR2) radiotherapeutic candidate for cancer.

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"The team at Ratio is honored and excited to partner with Novartis on the development of a next-generation SSTR2-targeting therapeutic," said Jack Hoppin, Ph.D., Chief Executive Officer of Ratio. "Together, we aim to develop a best-in-class therapy in the fight against SSTR2-expressing tumors."

"Radioligand therapies hold transformative potential for certain forms of cancer, and Novartis is committed to maximizing their impact by continually improving the benefit for patients," said Fiona Marshall, President of Biomedical Research at Novartis. "We are delighted to collaborate with Ratio to advance this RLT candidate and work together to bring forward additional therapeutic options for patients with difficult-to-treat cancer."

Under the terms of the agreement, Ratio will receive combined upfront and potential milestone payments up to $745m, and is eligible to receive tiered royalty payments. Ratio will collaborate with Novartis to drive preclinical activities to research and select an SSTR2-targeting development candidate. Novartis will assume responsibility for all remaining development, manufacturing, and commercialization activities.

The collaboration combines the expertise and strengths of Ratio and Novartis to further elevate the safety and efficacy of radiopharmaceuticals for patient benefit.

Chestnut Partners served as exclusive financial advisor to Ratio for this transaction.

On November 18, 2024 Orphelia Pharma, a pharmaceutical company dedicated to the development and marketing of pediatric and orphan medicines, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a negative opinion on the Marketing Authorization Application for KIZFIZO (temozolomide oral suspension) for the treatment of patients with relapsed or refractory high-risk neuroblastoma, because the CHMP considered that a positive benefit-risk balance has not been established at this stage (Press release, ORPHELIA Pharma, NOV 18, 2024, View Source [SID1234648474]). Orphelia will seek a re-examination of the opinion by the CHMP.

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"We are extremely disappointed by the CHMP’s negative opinion and understand that this may also be disappointing for the pediatric oncology community as well as for parents of children suffering from cancer." said Jérémy Bastid, Chief Medical Officer at Orphelia Pharma. "There is a significant demand for developing children-adapted formulations. Orphelia Pharma has been developing KIZFIZO in collaboration with Gustave Roussy, the leading European cancer center, for the last seven years specifically to address this unmet medical need for a drinkable temozolomide medication in the treatment of relapsed or refractory neuroblastoma, which affects very young children".

"As part of the re-examination process, we will seek to address the CHMP’s grounds for refusal and we will work diligently to substantiate the clinical benefit of the treatment so that KIZFIZO can be available to pediatric patients in the EU without further delay" commented Laurent Martin, Chief Pharmaceutical Affairs Officer at Orphelia Pharma.

In the meantime, Orphelia Pharma will, subject to agreement by the relevant authorities, continue to make KIZFIZO available to pediatric patients suffering from relapsed or refractory neuroblastoma under compassionate use or early access programs as well as to patients enrolled into ongoing clinical trials.

About KIZFIZO 40 mg/ml

KIZFIZO (temozolomide oral suspension, 40 mg/ml) is a ready-to-use oral liquid pediatric formulation of temozolomide developed/designed specifically for use in the treatment of children with relapsed or refractory high-risk neuroblastoma, which carries a very poor prognosis. This age-adapted and taste-masked formulation delivers an accurate dose in a small volume, while avoiding drug handling and caregiver exposure to temozolomide. It is the result of a collaboration between the pharmacists and clinicians at Gustave Roussy hospital and the development team at Orphelia Pharma.

In March 2022, KIZFIZO was granted Early Access Authorization (Autorisation d’Accès Précoce) by the French authorities, for the treatment of refractory and relapsed neuroblastoma as monotherapy or in combination with irinotecan or topotecan.

KIZFIZO has received Orphan Drug Designation (ODD) from the EMA and the FDA, the formulation is covered by granted patents and pending applications in Europe and the US.

The pharmacokinetics of KIZFIZO in children have been evaluated in TEMOkids, a European multicenter population pharmacokinetic acceptability and safety study in pediatric patients in need of temozolomide (NCT04610736).

Efficacy and safety data for temozolomide in relapsed or refractory neuroblastoma submitted in the application includes in particular:

BEACON-Chemo, a sub-analysis of the chemotherapy arms of the BEACON study, a prospective randomized phase II study in refractory or relapsed neuroblastoma. This study was sponsored by Birmingham University (UK).
Retro-TMZ, a multicenter descriptive, retrospective study, assessing the efficacy and tolerability of temozolomide in children with refractory or relapsed neuroblastoma. This study was conducted by Gustave Roussy (France).
About Neuroblastoma

Neuroblastoma is the most common extracranial cancer in early childhood, with approximately 900 new cases diagnosed per year in the European Union. It almost exclusively affects children under five, with a median age at diagnosis of 18 months. Neuroblastoma has a wide diversity of clinical outcomes, which is reflected in the risk stratification. Approximately 40% of patients have the high-risk disease and often face a poor response to first line induction therapy or later relapse. There remains a high unmet need for relapsed or refractory neuroblastoma patients and the best therapeutic strategy is still an intensive area of research. Temozolomide is the standard chemotherapy and is therefore an essential part of the treatment armamentarium for these patients.

On November 18, 2024 OncoSpherix, Inc., a preclinical-stage cancer drug development company advancing HIF inhibitors for a variety of cancer indications, reported participation in the 2024 Georgia Bio Life Sciences Summit last month from October 21 to October 22, 2024, where the company was featured in the prestigious Company Showcase (Press release, OncoSpherix, NOV 18, 2024, View Source [SID1234648473]). This event provided a valuable platform for OncoSpherix to present its pioneering developments in cancer therapies and underscore its commitment to advancing cancer treatment.

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The Georgia Bio Life Sciences Summit, known for bringing together key players in the biotechnology and life sciences sectors, offered OncoSpherix an opportunity to engage with industry leaders, investors, and researchers. The Company Showcase spotlighted OncoSpherix’s unique approach to precision oncology, focusing on therapies designed to block activation of HIF and combat hard-to-treat cancers more effectively.

"We are honored to have been part of the Company Showcase at the 2024 Georgia Bio Life Sciences Summit," said OncoSpherix CEO, Margaret Offermann, MD, PhD. "This platform allowed us to share our breakthroughs in developing new drugs for oncology and our mission to bring innovative, effective therapies to patients in need. The positive response from the community reinforces our commitment to developing solutions that will make a significant impact on cancer treatment."

On November 18, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported new findings supporting the ability of Annamycin to overcome resistance to Venetoclax in acute myeloid leukemia ("AML") (Press release, Moleculin, NOV 18, 2024, View Source [SID1234648472]). This includes data from preclinical in vitro studies recently accepted for online publication at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting, and correlates with efficacy demonstrated by recent preliminary clinical data in subjects who were relapsed from or refractory to first line Venetoclax regimens and were then treated with Annamycin in combination with Ara-C ("AnnAraC").

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Jorge Cortes, MD, Director of the Georgia Cancer Center at Augusta University and a member of the Company’s Scientific Advisory Board, commented, "Although Venetoclax has been an important improvement in first line therapy for AML patients who are unfit for intensive chemotherapy, the rate of relapse is high and overall survival post relapse is just a few months. This turns out to be a large percentage of AML patients in total and we clearly need a better treatment option."

Michael Andreeff, MD, PhD, Professor of Medicine, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center and a member of the Company’s Scientific Advisory Board, added, "Many patients get Ven-Aza, not because they are ‘unfit’ but because of the high initial response rates. When they relapse, however, our options are very limited. Annamycin combined with Ara-C could significantly advance the standard of care and provide better outcomes for these high-risk patients. I am excited to be a part of the next step in the development of this important asset."

A prior publication, Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens1, reported that the CR/CRi2 rate for salvage therapy using available standard of care in AML subjects who relapsed from or were refractory to Venetoclax regimens was 12.5% (n=24, 4% CR). The new preliminary clinical findings announced today in the MB-106 clinical trial indicate that relapsed or refractory ("R/R") AML subjects previously treated with Venetoclax regimens achieved a 60% CR/CRi rate (n=5, 40% CR), more than 4 times the rate that would be expected based on the above referenced paper. As previously disclosed in MB-106, there was an overall CR/CRi rate of 60% (50% CR) in 2nd line subjects (n=10) and 41% (36% CR) in all subjects, 1st-7th line (n=22).

An abstract titled, "Annamycin, a non-cardiotoxic anthracycline, demonstrates unique organotropism and activity against Ara-C and Venetoclax resistant AML," supporting the clinical activity of Annamycin was accepted for online publication at the ASH (Free ASH Whitepaper) Annual Meeting being held December 7-10, 2024, in San Diego, CA. The abstract will be published in a supplemental issue of Blood, expected in late November, and will become part of the permanent ASH (Free ASH Whitepaper) and Blood abstracts archive following the conclusion of the Annual Meeting.

Additionally, new preliminary data from the Company’s Phase 1B/2 clinical trial evaluating AnnAraC for the treatment of subjects with AML as both first line therapy and for subjects who were refractory to or relapsed after induction therapy (MB-106) demonstrated median overall survival ("OS") of 9.1 months for subjects with a wide range of (0-6) prior lines of therapy (n=22) and 11.6 months (n=10) for subjects with 1 prior line of therapy (second line therapy).

"Moleculin is focusing on development of Annamycin to address the significant unmet need in R/R AML. The growing body of preliminary data continue to bolster our confidence in the safety and efficacy of Annamycin, and its potential to provide patients and physicians with a promising new treatment option in AML," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "We believe the latest preliminary OS data we are seeing in our MB-106 trial can now be considered exceptional and we look forward to the initiation of our pivotal registration study, especially now that our recent protocol amendment allows for disclosing unblinded data for the first 45 subjects, which we expect within the next 12 months."

The Company is advancing the development of Annamycin in a Phase 3 pivotal trial evaluating AnnAraC for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML) (MB-108). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) will be a global trial, including sites in the US. The Company remains on track to initiate patient treatment in the first quarter of 2025.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA).

On November 18, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported abstracts detailing selinexor data have been selected to be presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 7-10, 2024 in San Diego, CA (Press release, Karyopharm, NOV 18, 2024, View Source [SID1234648471]).

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"We are pleased to share presentations on selinexor at this year’s annual meeting," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research at Karyopharm. "The data being presented demonstrate our commitment, as well as that of our partners to our ongoing work in multiple myeloma and myelofibrosis."

Details for the ASH (Free ASH Whitepaper) 2024 selected Karyopharm abstracts are as follows:

Abstract Title

Presentation Type

Abstract #

Session Date/Time

Multiple Myeloma

Efficacy and Safety of Selinexor, Pomalidomide, and Dexamethasone (SPd) for Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Poster

1996

Saturday, December 7, 2024

5:30pm – 7:30pm PST/ 8:30pm – 10:30pm EST

Myelofibrosis

Selinexor Depletes Ruxolitinib Refractory Myelofibrosis Hematopoietic Stem Cells By Inducing Apoptosis and Blunting the Pro-Inflammatory Milieu

Poster

1377

Saturday, December 7, 2024

5:30pm – 7:30pm PST/ 8:30pm – 10:30pm EST

Details for a selected partner presentation on Antengene’s latest data are as follows:

Abstract Title

Presentation Type

Abstract #

Session Date/Time

Multiple Myeloma

Weekly Selinexor, Bortezomib and Dexamethasone (SVd)
Versus Twice Weekly Bortezomib and Dexamethasone (Vd) in Chinese Patients with Relapsed and Refractory Multiple Myeloma: Primary Analysis of Phase 3 Bench Study

Poster

4748

Monday, December 9, 2024

6:00pm – 8:00pm PST/

9:00pm – 11:00pm EST

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 a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. 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 the United States:

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.