On March 7, 2024 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported full year 2023 financial results and provided a corporate update (Press release, Alpha Tau Medical, MAR 7, 2024, View Source [SID1234640913]).

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"2023 was an incredibly productive year, as we launched our ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma, which is expected to complete recruitment in the second half of 2024, and as we initiated a number of feasibility trials in difficult-to-treat internal organ tumors with high unmet need," stated Alpha Tau CEO Uzi Sofer. "We saw meaningful inflection points delivered by the end of 2023, including strong interim safety and feasibility data from our pancreatic cancer trial in Montreal, with initial signs of dose response, and our PMDA submission in Japan for pre-market approval. In parallel, we continue to advance our commercial planning activities and to solidify our supply chain, which was recently bolstered by both a valuable land grant in Jerusalem that is expected to increase our future manufacturing capacity, as well as by the leasing of a second manufacturing site in the United States. In 2024, we are focused on completing patient recruitment in our U.S. pivotal ReSTART study and our pancreatic cancer pilot study in Canada, and on beginning to treat patients in studies targeting a number of other internal organs. We are also exploring the addition of new clinical trials in the U.S., based upon recent positive regulatory feedback. We expect to begin work on the construction of our second U.S. facility, in Hudson, NH, and on the construction plans for our second facility in Jerusalem. Alpha Tau expects to remain adequately capitalized to support all of these programs over the coming years."

Recent Corporate Highlights:

● In October, the Company announced that it had entered into a long-term lease agreement for a standalone building of over 14,000 rentable square feet in Hudson, NH, with the intention of erecting the Company’s second U.S. manufacturing site, alongside its first site in nearby Lawrence, MA.

● In October, the Company announced that Dr. Stephen Hahn, a former commissioner of the U.S. Food and Drug Administration ("FDA") and a distinguished expert in the field of radiation oncology and translational clinical research, joined its Scientific Advisory Board.

● In November, the Company announced that Japan’s Pharmaceuticals and Medical Devices Agency ("PMDA") accepted Alpha Tau’s submission requesting shonin pre-market approval of Alpha DaRT in patients with recurrent head and neck cancer, following multiple pre-submission consultation meetings with the PMDA per common practice in Japan.

● In November, the Company announced interim results from treatment of the first five patients in the Company’s safety and feasibility trial in Montreal, Canada, examining the use of Alpha DaRT to treat advanced pancreatic cancer. The Alpha DaRT procedure was deemed technically successful in all five cases, with Alpha DaRT sources successfully inserted into the target tumors. There were no reported serious adverse events deemed related to the product, and the only reported adverse events deemed possibly related to the product were of severity grade 1 (mild). In addition, despite the conservative and gradual step-up of tumor coverage from minimal initial levels, three of the five patients demonstrated stable disease responses at four weeks after treatment, and one was upgraded to partial response at 69 days after treatment.

Upcoming Milestones

● Planning treatment of the first patient in the Canadian liver metastases safety and feasibility trial in H1 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Planning treatment of the first patient in the Israeli recurrent lung cancer safety and feasibility trial in H1 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Targeting first brain cancer treatment in H2 2024.

● Targeting completion of patient recruitment in the ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma in H2 2024. For more information please see here: View Source

● Targeting completion of patient recruitment in the Canadian advanced inoperable pancreatic cancer study in Montreal in H2 2024. For more information please see here: View Source

● Anticipating response from PMDA in Japan by year-end 2024 for pre-market approval for Alpha DaRT in patients with recurrent head and neck cancer.

Financial results for the full year ended December 31, 2023

R&D expenses for the year ended December 31, 2023 were $26.4 million, compared to $20.9 million in 2022, due to increased employee headcount, compensation and benefits, including share-based compensation, increased operating costs, and increased pre-clinical study and clinical trial expenses, particularly in our U.S. ReSTART trial, with a smaller offset through government grants from the Israel Innovation Authority.

Marketing expenses for the year ended December 31, 2023 were $1.9 million, compared to $1.0 million for 2022 due to increased employee compensation and benefits, including share-based compensation, and the hiring of our chief commercial officer.

G&A expenses for the year ended December 31, 2023 were $7.3 million, compared to $10.3 million for 2022, due to to decreased professional fees (including D&O insurance), and costs associated with our financing transaction in the first quarter of 2022.

Financial expenses (income), net, for the year ended December 31, 2023 were $(6.5) million, compared to $1.6 million for 2022, due to revaluation of warrants and an increase in interest from bank deposits, offset by changes in foreign exchange rates.

For the year ended December 31, 2023, the Company had a net loss of $29.2 million, or $0.42 per share, compared to a net loss of $33.8 million, or $0.53 per share, in 2022.

Balance Sheet Highlights

As of December 31, 2023, the Company had cash and cash equivalents, restricted cash and deposits in the amount of $84.9 million, compared to $105.4 million as of December 31, 2022 and $90.1 million as of September 30, 2023. The Company expects that this cash balance will be sufficient to fund operations for at least two years.

About Alpha DaRT

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by intratumoral delivery of radium-224 impregnated sources. When the radium decays, its short-lived daughters are released from the sources and disperse while emitting high-energy alpha particles with the goal of destroying the tumor. Since the alpha-emitting atoms diffuse only a short distance, Alpha DaRT aims to mainly affect the tumor, and to spare the healthy tissue around it.

On March 7, 2024 Alligator Bioscience AB ("Alligator") (Nasdaq Stockholm: ATORX) and Aptevo Therapeutics ("Aptevo") (Nasdaq: APVO) reported positive interim data from the dose escalation phase of their Phase 1 trial evaluating ALG.APV-527 for the treatment of solid tumors likely to express the tumor antigen 5T4 (Press release, Alligator Bioscience, MAR 7, 2024, View Source [SID1234640912]).

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The multi-center, dose escalation trial is now more than 50% enrolled, and preliminary results include:

Treatment was overall well-tolerated, and a maximum tolerated dose has not yet been determined, dose-escalation in higher-dose cohorts is ongoing
ALG.APV-527 could be measured in all patients with plasma concentration of ALG.APV-527 consistent with the administered dose
Biomarker analyses indicate the expression of the targets (4-1BB and 5T4) in tumor biopsies and confirm biological activity of ALG.APV-527
Of particular interest, signs of clinical activity were observed for both enrolled patients with heavily pre-treated breast cancer. These patients demonstrated measurable level of drug in circulation (pharmacokinetics) and reproducible elevation of serum pharmacodynamic markers with dosing, suggesting the drug is biologically active. One patient remained on study for seven months and a second remains on study beyond nine months. Both patients achieved best overall response of stable disease.

"I am pleased to share that we are now dosing cohort four, heading into higher dose ranges where we believe there is potential for increased signs of clinical activity based on preclinical models. We have treated patients with multiple tumor types including breast, pancreatic, non-small cell lung cancer and colorectal cancer. It is our belief that continued analysis of this cross section of tumor types will offer important insights about ALG.APV-527 that can be used to increase our success in later stage development," said Dirk Huebner, MD, Chief Medical Officer at Aptevo. "Additionally, as the trial has progressed, we have seen growing enthusiasm among our clinical sites, evidenced by a long and growing waiting list of patients who would like to participate in the study. We look forward to announcing additional data later in the year."
"We’re thrilled to share positive interim Phase 1 data from our trial with ALG.APV-527, a testament to our dedicated collaboration with Aptevo. The presence of both targets in tumor biopsies is a particularly encouraging finding, which underlines the potential of our novel bispecific antibody to treat multiple indications," said Sumeet Ambarkhane, MD, CMO at Alligator Bioscience. "We very much look forward to continuing this journey together, to make a meaningful impact in the fight against cancer."
About the Trial
The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label trial that will include six cohorts (dose levels) in a 3+3 design*. The trial will be conducted at up to 10 sites in the U.S. among adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial will assess the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.

*The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level.

About ALG.APV-527
ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer.

Preclinical studies, highlighting the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in preclinical models, were recently published in the peer-reviewed publication, Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

On March 7, 2024 Merck, a leading science and technology company, reported financial results for 2023 in line with its guidance published in August despite a challenging market environment, thus demonstrating the robustness of its business model (Press release, Merck KGaA, MAR 7, 2024, View Source [SID1234640888]). The strong development of the Healthcare business sector partly compensated for the market-related declines in sales and earnings in Life Science and Electronics. The company expects to gradually return to organic growth in the course of fiscal 2024.

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On March 6, 2024 Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, reported the company will present data on its oncology program targeting flap endonuclease 1 (FEN1), a structure-specific metallonuclease that cleaves 5’ DNA flaps during replication and repair, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, taking place April 5-10 at the San Diego Convention Center, San Diego CA (Press release, Blacksmith Medicines, MAR 6, 2024, View Source [SID1234643533]).

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Details of the poster presentation are as follows:

Abstract Number: 7148

Title: "Small molecule inhibitor of FEN1 nuclease utilizing a novel metal binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR"

Session Category: Experimental and Molecular Therapeutics

Session Title: Novel Antitumor Agents 6

Session Date and Time: Wednesday April 10, 2024 9:00 AM – 12:30 PM

Location: Poster Section 23

Poster Board Number: 10

The abstract is now available on the conference website at AACR (Free AACR Whitepaper) Annual Meeting 2024.

About FEN1

Flap endonuclease 1 (FEN1) is a structure-specific di-magnesium metallonuclease that cleaves 5’ DNA flaps during replication and repair. FEN1 is an attractive target for development of anticancer therapeutics because it is overexpressed in many tumor types and has a large number of synthetic lethality partners including genes in Homologous Recombination (HR) pathway.

About metalloenzymes and the Blacksmith platform

Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following:

A large proprietary fragment library of metal-binding pharmacophores (MBPs);
A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease;
A first-of-its-kind metallo-CRISPR library of custom single guide RNAs;
An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and
A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines.

On March 6, 2024 Ono Pharmaceutical reported that it has entered into a license agreement with NEX-I, Inc. (Seoul, Republic of Korea; CEO, Kyoung Wan Yoon; "NEX-I") for NXI-101 (Press release, Ono, MAR 6, 2024, View Source [SID1234641879]).

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NXI-101 is a first-in-class antibody drug candidate targeting ONCOKINE-1, which is a cancer immunotherapy-resistant factor discovered by NEX-I through its proprietary target screening platform "ONCOKINE platform". It has a potential to be a novel antibody drug with an efficacy against multiple cancer types including cancer immunotherapy-resistant cancer.

Under the terms of this agreement, Ono will have an exclusive right to develop and commercialize NXI-101 and its backup antibodies worldwide. Ono will pay to NEX-I an up-front and milestone payments on the progress of development and commercialization, as well as tiered royalties based on net sales.

"We are pleased to collaborate with NEX-I having a proprietary ONCOKINE platform for development and commercialization of NXI-101. We expect NXI-101 to be a new treatment option for cancer patients," said Toichi Takino, Senior Executive Officer / Executive Director, Discovery & Research of Ono. "Leveraging Ono’s experience and expertise in cancer immunotherapy, we will work on the development of the compound to add it to our development pipeline in oncology."

"We are delighted to start a journey with Ono, a leader in cancer immunotherapy well-known for its breakthrough anti-PD-1 antibody. This collaboration aligns with NEX-I’s strategic focus on novel target discovery and the advancement of our flagship tumor microenvironment modulator, NXI-101. Through this landmark partnership, we underscore our commitment to identifying and developing novel and differentiated therapies that promise substantial benefits for patients," said Kyoung Wan Yoon, Ph.D., Chief Executive Officer of NEX-I. "Our alliance with Ono represents a significant step forward for our ONCOKINE platform to assemble a diverse portfolio of clinical candidates across a broad range of mechanisms and therapeutic targets."