On June 17, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported that an abstract detailing the first ever preclinical data from the combination of menin inhibitors with Actinium’s ARC Actimab-A in acute myeloid leukemia (AML) models was presented at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Congress held June 13 – 16, 2024, in Madrid, Spain (Press release, Actinium Pharmaceuticals, JUN 17, 2024, View Source [SID1234644403]). Actinium studied Actimab-A in combination with the leading menin inhibitors, revumenib (Syndax Pharmaceuticals, Inc.) and ziftomenib (Kura Oncology, Inc.), which are being developed for patients with KMT2A rearrangements and NMP1 mutations, which are present in approximately 10% and 30% of AML patients, respectively.

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Actimab-A + Menin inhibitor combination results include:

Actimab-A as a single agent showed potent in vitro AML cell killing activity in both MV-4-11 and MOLM-13 KMT2A mutant cell lines, compared to the non-radio conjugated CD33 antibody lintuzumab (p<0.0001)

Actimab-A enhanced AML cell death when combined with both revumenib and ziftomenib at all dose levels in difficult to treat KMT2A mutant AML

The combination of Actimab-A with leading menin inhibitors triggered an acute increase in AML necrosis and cell death in vivo relative to single agent therapy within 72 hours of dosing

Anti-tumor effect was significantly potentiated and prolonged when combining Actimab-A with a leading menin inhibitor compared to monotherapies in xenograft leukemia models in vivo (p<0.0024 Actimab-A + menin) as shown in the exhibit below
The Actimab-A + Menin Inhibitor combination presentation can be accessed on the investor relations page of Actinium’s website here.

Actimab-A targets CD33, a marker expressed ubiquitously in patients with AML, and is conjugated with the alpha-partible payload Actinium-225. The broad expression of CD33 and the differentiated mutation agnostic cell-killing mechanism of targeted radiotherapy make Actimab-A broadly applicable for combinations with chemotherapy, targeted agents including venetoclax, FLT3 and menin inhibitors, immunotherapies and cellular therapies supporting its potential backbone therapy profile across the AML patient treatment journey.

Sandesh Seth, Actinium’s Chairman and CEO, said, "Combining with menin inhibitors is an exciting expansion of the already broad potential of Actimab-A in AML. Across single agent and combination studies, Actimab-A has produced high rates of response, MRD negativity and improved survival in high-risk, relapsed and refractory patients including those with a TP53 mutation and venetoclax failures. The broad expression of CD33 in AML coupled with the potency of Actinium-225 make Actimab-A an ideal agent for treating radiation sensitive AML. We are encouraged by this highly promising initial data and the synergistic potential of Actimab-A with menin inhibitors, which has broad potential across the AML treatment continuum including frontline, maintenance and relapsed/refractory settings. We are eager to continue to study this combination and generate additional data that could support advancing into clinical studies of Actimab-A with menin inhibitors."

Menin inhibitors are a class of drug candidates being developed for patients with AML that have a rearrangement of the KMT2A gene, previously known as the mixed-lineage leukemia (MLL) or mutation of the NPM1 gene. There are multiple menin inhibitors in development for these patients with revumenib (Syndax Pharmaceuticals, Inc.) being most advanced having a PDUFA data of September 2024 and ziftomenib (Kura Oncology, Inc.) enrolling patients in a registration Phase 2 trial. Multiple menin inhibitors are being studied in Phase 1 clinical trials by companies including Johnson & Johnson, Sumitomo Pharma Co., Ltd., Hutchmed, Biomea Fusion, Inc. and BioNova Pharmaceuticals Pvt Ltd.

On June 17, 2024 ReviR Therapeutics, a biotechnology company specializing in the development of small molecule RNA splicing modulators for neurogenetic diseases and oncology indications, and Asieris Pharmaceuticals, a global biopharmaceutical leader in the discovery, development, and commercialization of innovative drugs for genitourinary tumors and related diseases, reported that a milestone was reached in their ongoing collaboration (Press release, Asieris Pharmaceuticals, JUN 17, 2024, View Source [SID1234644402]). The joint effort to develop treatments for cancers using a novel target has resulted in the successful identification of a new lead series of small molecules that modulate the expression of an oncogenic driver gene. The molecules were discovered using ReviR’s proprietary VoyageR AI platform which has the potential to revolutionize therapeutic discovery across multiple indications, including genitourinary cancers.

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The collaboration successfully completed the first milestone of target engagement, and demonstrated that a series of molecules from ReviR’s proprietary compound library are capable of driving inclusion of a cryptic exon into the mRNA of a novel target gene, thus resulting in subsequent reduction of the disease protein. This discovery advances the development of a novel therapy for genitourinary cancers one step closer to clinical development. ReviR’s VoyageR AI platform offers significant advantages to characterize small molecule splicing modulators, including target identification as well as enhanced potency and specificity assessments across genomes. This platform holds immense promise for the development of novel treatments for a broad spectrum of genetic diseases including Huntington’s Disease, which is a key focus for ReviR’s pipeline development.

"We are very pleased with what our team, alongside our esteemed collaborators at ReviR Therapeutics, has accomplished. This milestone demonstrates the value of teamwork in accelerating advancements in drug discovery," said Alice Chen, Senior Vice President of Discovery Biology & Head of Translational Research at Asieris Pharmaceuticals.

Peng Yue, PhD, CEO of ReviR Therapeutics, said, "Today marks a significant milestone in our journey to develop a new therapy for cancers with limited treatment options. This breakthrough in splicing modulator technology brings us one step closer to bringing much-needed relief to patients."

Both companies are evaluating the option to further discover and develop novel small molecule splicing modulators towards novel targets and exploring the potential of expanding VoyageR to various therapeutic applications. This collaboration exemplifies the power of joint efforts in driving innovation within the field of splicing modulators and paving the way for a future with more effective treatments for genetic diseases and targeted oncology therapies.

On June 17, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS) ("iTeos"), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, and its development partner GSK, reported to have initiated the first, global Phase 3 registration study of belrestotug + dostarlimab doublet versus placebo + pembrolizumab in patients with previously untreated, unresectable, locally advanced or metastatic PD-L1 selected non-small cell lung cancer (NSCLC) (Press release, iTeos Therapeutics, JUN 17, 2024, View Source [SID1234644400]).

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"With the initiation of the first Phase 3 study for belrestotug, we are entering a monumental stage in our journey to develop a world-leading oncology company. Nearly 70% of patients with first-line PD-L1 high non-small cell lung cancer rely upon a chemotherapy-free regimen. We believe belrestotug + dostarlimab are poised to potentially advance the therapeutic regimen in this setting and establish new benchmarks," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "Based on our high-quality doublet exceeding its pre-defined efficacy criteria for clinically relevant activity in an interim assessment from the Phase 2 GALAXIES Lung-201 study, we believe initiating the Phase 3 program with this patient population will serve as the foundation to our broader strategy and marks our first step in building a franchise."

The randomized, double-blind, placebo-controlled, multicenter trial will enroll approximately 1,000 patients with previously untreated, unresectable, locally advanced or metastatic PD-L1 selected NSCLC in North America, South America, Europe and Asia. The primary endpoints of the trial are progression free survival and overall survival. In the GALAXIES Lung-301 trial, patients will be randomized 1:1 to either an intravenous infusion of the belrestotug + dostarlimab doublet or placebo + pembrolizumab.

In May 2024, iTeos announced an interim assessment of the Phase 2 GALAXIES Lung-201 study of the belrestotug + dostarlimab doublet in previously untreated, locally advanced, or metastatic PD-L1 selected NSCLC exceeded pre-defined efficacy criteria for clinically relevant activity and showed an acceptable safety profile in line with the TIGIT:PD-1 class. Clinically meaningful tumor reduction was observed at every belrestotug + dostarlimab dose vs dostarlimab monotherapy.

On June 17, 2024 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that on June 12, 2024 it entered into an exclusive license from Roswell Park Comprehensive Cancer Center for a portfolio of dendritic cell technologies and intellectual property (IP) (Press release, Northwest Biotherapeutics, JUN 17, 2024, View Source [SID1234644399]). The technologies are already in Phase 2 clinical trials, and the Company plans to collaborate with the lead scientist-clinician, Dr. Pawel Kalinski, on the further development of the technologies. The license is the culmination of more than 2 years of discussions and negotiations.

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The license includes 5 new patent families that were just filed in 2023 and hence have their full potential patent life ahead of them. The technologies include enhanced versions of dendritic cells (DCs) and DC based therapies, as well as conditioning regimens designed to enhance patient responses and approaches to reprogram the tumor microenvironment to boost immune therapies and help overcome resistance to checkpoint inhibitors.

The DC based therapies include versions with tumor antigens loaded into the DCs and versions for intra-tumoral administration without pre-loading of antigens. Phase 2 trials involving the licensed technologies for two different cancers opened for enrollment earlier this year and are currently under way, and a third Phase 2 trial for a third cancer is pending. The trials are fully funded by grant funding and are being conducted as investigator led trials. The Company does not anticipate having to provide any funding or undertake any operational role for these trials.

As previously reported, over time the Company has been quietly in-licensing various technologies and IP from various institutions and entities which it believes can be valuable in building a leading franchise in dendritic cell therapies.

The portfolio in-licensed from Roswell Park is complementary to, and builds upon, a portfolio which the Company exclusively licensed from another institution last year. Together, the two portfolios encompass more than 20 years of work by one of the foremost groups of dendritic cell experts, led by Dr. Kalinski.

The portfolio in-licensed last year includes the foundational technologies and IP, and positive early-stage clinical trial results, developed by the Kalinski group over 17 years before coming to Roswell. The portfolio in-licensed now includes the further work during the last 7 years at Roswell. Taken together, the Company believes that the two portfolios comprise a whole that is greater than the sum of its parts and offer compelling synergies with the Company’s own portfolio. The Company plans to collaborate with Dr. Kalinski on the further clinical development of the combined technologies.

The Company believes that the infrastructure and systems it has developed, and experience it has gained, in producing and delivering personalized living-cell DC based therapies for large numbers of patients make it uniquely positioned to help accelerate the late-stage development of the licensed DC technologies. The Company’s 331-patient Phase 3 clinical trial remains one of the largest personalized cell therapy trials conducted to date, and the Company’s extensive experience treating compassionate use patients has added valuable ongoing "real world" experience.

"We are excited to join forces with Dr. Kalinski, one of the foremost experts on dendritic cell biology and therapies," commented Linda Powers, the Company’s CEO. "We also greatly appreciate the supportiveness of the institutions throughout the long process of working out the arrangements to keep the Kalinski portfolios intact and to license them to NWBio. In the immediate term, we will continue to focus intensively on pursuing the approval and commercialization of DCVax-L for glioblastoma, but we are excited to begin working on growth opportunities with the licensed technologies as well."

The terms of the Roswell license include standard provisions for an upfront license fee and milestones related to the first Phase 2 trial, first Phase 3 trial, first product approval and first commercial sale. If all of the milestones are met, the payments would be approximately $2.3 million. The license terms also include royalties of 4% on product sales (potentially reduced to 3% in the event of royalty stacking).

On June 17, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that it has commenced an underwritten public offering, subject to market and other conditions, to issue and sell its ordinary shares and pre-funded warrants (Press release, UroGen Pharma, JUN 17, 2024, View Source [SID1234644396]). In connection with the proposed offering, UroGen also expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the total number of ordinary shares (including those underlying pre-funded warrants) offered in the public offering. There can be no assurance as to whether or when the proposed offering may be completed, or as to the actual size or terms of the proposed offering. All of the ordinary shares and pre-funded warrants to be sold in the proposed offering will be offered by UroGen.

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TD Cowen and Guggenheim Securities are acting as joint book-running managers for the proposed offering. Oppenheimer & Co. is acting as lead manager for the proposed offering. Ladenburg Thalmann is acting as co-manager for the proposed offering.

The proposed offering is being made pursuant to a shelf registration statement on Form S-3, including a base prospectus, filed with the Securities and Exchange Commission (the "SEC") and declared effective on November 29, 2022. A preliminary prospectus supplement and accompanying prospectus relating to the proposed offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement (when available) and accompanying prospectus may be obtained by contacting TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, NY 10017, by telephone at (855) 495-9846 or by email at [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017, telephone: (212) 518-5548, email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.