On February 12, 2024 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported the initiation of the Phase 2 portion of ALKOVE-1, its Phase 1/2 clinical trial of NVL-655 for patients with ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors, following alignment with the US Food and Drug Administration (FDA) on a recommended Phase 2 dose (RP2D) of 150 mg once daily (QD) (Press release, Nuvalent, FEB 12, 2024, View Source [SID1234639987]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

NVL-655 is a novel brain-penetrant ALK-selective tyrosine kinase inhibitor (TKI) created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family that may limit the use of currently available ALK TKIs.

In the Phase 1 portion of ALKOVE-1, six dose levels (15 mg to 200 mg QD) of NVL-655 were evaluated in heavily pre-treated patients with ALK-positive solid tumors, and a maximum tolerated dose was not reached. The RP2D of 150 mg QD maintained steady state plasma levels above target efficacy thresholds (ALK wild type fusions and ALK single and compound mutations in both the periphery and in the CNS).

"The transition of our NVL-655 program into Phase 2 advances a second, parallel opportunity towards our goal of bringing potential best-in-class therapies to patients as efficiently as possible," said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. "This sense of urgency is reflected in the thoughtful design of the Phase 2 portion of the ALKOVE-1 trial which aims to accelerate the clinical investigation that may support a potential marketing application towards an initial approval for previously treated patients with ALK-positive NSCLC. The Phase 2 portion also includes a TKI-naïve cohort which may provide an opportunity to generate early data, and could be conducted in parallel with a front-line registration-directed trial."

Ms. Noci continued, "Support for the design of the Phase 2 cohorts includes the broad clinical activity and favorable tolerability observed to date in heavily pre-treated patients in the Phase 1 portion of ALKOVE-1. Combined with the demonstrated nonclinical activity of NVL-655 in the periphery and in the CNS, and its selective inhibition of ALK and ALK single and compound drug-resistance mutations over the structurally-related TRK kinases, we believe there is the potential for NVL-655 to provide durable responses while minimizing adverse events and dose limiting toxicities for patients with ALK-positive cancers throughout the treatment paradigm."

"With today’s announcement, we’ve delivered on the first of the key 2024 milestones laid out in our OnTarget 2026 operating plan, an achievement made possible by the tireless dedication of our team to our mission of delivering precisely targeted therapies to patients with cancer," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "With all of our programs, our goal is to not only address the existing medical needs for later-line patients but to ultimately deliver therapies that can move up the treatment paradigm, and our multi-pronged development strategy for NVL-655 exemplifies this approach. We look forward to sharing an update from the ALKOVE-1 trial as well as more detail on our broader front-line development strategy for ALK later this year."

ALKOVE-1 Phase 2 Design

The Phase 2 portion of the ALKOVE-1 trial will be conducted globally across North America, Europe, Asia, and Australia. The single arm, open label Phase 2 portion is designed with registrational intent for TKI pre-treated patients with ALK-positive NSCLC and to enable preliminary investigation for patients with ALK-positive NSCLC who are TKI naïve. The Phase 2 cohorts are designed to evaluate NVL-655 in:

TKI Pre-Treated ALK-Positive NSCLC
2 – 3 Prior TKIs: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs. Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
1 Prior 2G TKI: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior second-generation (2G) ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
1 Prior 3G TKI: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib (third-generation, 3G) as the only prior ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed.
TKI-Naïve ALK-Positive NSCLC
Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.
Other
Other ALK-Positive NSCLC: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
Other ALK-Positive Solid Tumors: Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.
Additional details can be found on www.clinicaltrials.gov (NCT05384626).

Selection of NVL-655 RP2D

The selection of 150 mg QD as the RP2D for NVL-655 was supported by the FDA based on clinical data from the Phase 1 dose escalation portion of the ALKOVE-1 trial. The company believes that the preliminary Phase 1 data support the opportunity for NVL-655 as a potential best-in-class therapy that may be able to move up the treatment paradigm for patients with ALK-positive NSCLC.

The selection was based on the following considerations:

The dose level of 150 mg QD maintained steady state plasma levels above target efficacy thresholds (ALK wild type fusions and ALK single and compound mutations in both the periphery and in the CNS).
Favorable tolerability of NVL-655 was observed at the 150 mg QD dose level, continuing to suggest the potential for a highly ALK-selective, TRK sparing safety profile.
Early anti-tumor activity was observed in ALK-positive NSCLC patients across a broad range of doses, including 150 mg QD. Objective responses (RECIST 1.1) were observed in heavily pre-treated patients including patients who had received one or more second-generation TKIs (alectinib, brigatinib, or ceritinib) plus lorlatinib, patients who were lorlatinib-naïve, patients with ALK single and compound resistance mutations, and patients with CNS metastases.
Preliminary Phase 1 data were presented in October 2023, and the company expects to share an update from the ALKOVE-1 trial at a medical meeting in 2024.

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with both single or compound treatment-emergent ALK mutations such as G1202R. In addition, NVL-655 is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-655 has received orphan drug designation for ALK-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors.

About OnTarget 2026

OnTarget 2026 delineates Nuvalent’s 3-year operating plan towards bringing new, potential best-in-class medicines to patients with cancer. As part of this plan announced in January 2024, Nuvalent outlined the following anticipated milestones throughout 2024, leading to the company’s first potential pivotal data in 2025 and first potential approved product in 2026:

2024: Execute on Global Registrational Strategies
Progress the Phase 2 portion of the ARROS-1 trial of NVL-520 in patients with advanced ROS1-positive NSCLC with registrational intent;
Initiate the Phase 2 portion of the ALKOVE-1 trial of NVL-655 in patients with advanced ALK-positive NSCLC, including cohorts in pretreated patients with registrational intent;
Launch the front-line development strategy for its ALK program;
Present interim data from the ongoing ARROS-1 and ALKOVE-1 clinical trials at medical meetings; and,
Initiate the Phase 1 trial for its HER2 program.
2025: First Pivotal Data
2026: First Approved Product

On February 12, 2024 BioVaxys Technology Corp. (CSE: BIOV) (FRA: 5LB) (OTCQB: BVAXF) ("BioVaxys" or "Company") reported that it has executed the definitive Asset Purchase Agreement dated February 11th, 2024 to acquire the entire portfolio of discovery, preclinical and clinical development stage assets in oncology, infectious disease, antigen desensitization, and other immunological fields based on the DPX immune educating platform technology, developed by Canadian biotechnology company, IMV Inc., Immunovaccine Technologies Inc., and IMV USA ("IMV") (Press release, BioVaxys Technology, FEB 12, 2024, View Source [SID1234639986]). BioVaxys acquired the extensive technology portfolio from HIMV, LLC, an acquisition vehicle formed by Horizon Technology Finance Corporation (NASDAQ: HRZN) and IMV’s other secured creditors for the purpose of acquiring IMV’s intellectual property through a secured party credit bid in the proceedings commenced in Canada by IMV under the Companies’ Creditors Arrangement Act, R.S.C. 1985, c. C-36, as amended (the "CCAA").

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Horizon Technology Finance Corporation, an affiliate of Monroe Capital, is a leading specialty finance company that provides capital in the form of secured loans to companies in the technology, life science, healthcare information and services, and sustainability industries. Horizon is headquartered in Farmington, Connecticut, with a regional office in Pleasanton, California, and investment professionals located throughout the U.S.

Key transaction elements include a USD$750,000 upfront cash payment, various clinical development and regulatory milestone payments, a 15% share in license revenues, and a 6% gross sales royalty on product sales (such future gross sales royalties cancellable and extinguishable upon a one-time payment of USD$25,000,000 in cash) and shares of BioVaxys common stock with a deemed value of US$250,000, calculated at a price per share equal to the volume-weighted average price of the common shares during the 20 trading day period immediately prior to closing and will be subject to a hold period of four months and one day. HIMV will also be entitled to appoint an observer to BioVaxys’s Board of Directors.

The DPX antigen delivery platform acquired by BioVaxys is designed to stimulate a specific, coordinated and persistent anti-tumor immune response, improving the lives of patients with solid or hematological cancers. DPX can package a wide range of bioactive molecules in a single formulation, such as multiple nucleic acids/mRNA, proteins, peptides, virus-like particles, innate immune activators, and small molecules, to "feed" them to Dendritic Cells and Antigen Presenting Cells (or "APC’s") to stimulate a specific immune response.

The transaction supplements BioVaxys’ existing cancer vaccine portfolio with the addition of maveropepimut-S (MVP-S), a DPX-formulated cancer vaccine that delivers antigenic peptides from survivin, a cancer antigen commonly overexpressed in advanced cancers. MVP-S also delivers an innate immune activator and a universal CD4 T cell helper peptide. These elements foster maturation of antigen presenting cells as well as robust activation of CD8 T cell effector and memory function. Maveropepimut-S was recently in Phase IIB clinical trials for advanced Relapsed-Refractory Diffuse Large B Cell Lymphoma (DLBCL) and platinum resistant ovarian cancer, and is being clinically evaluated in bladder and breast cancer. In prior clinical studies, MVP-S treatment has been well tolerated and has demonstrated favorable clinical outcomes in multiple cancer indications as well as the activation of a targeted and sustained, survivin-specific anti-tumor immune response. Most recently, data were presented by IMV at the 2023 SGO Annual Meeting on Women’s Cancer on a phase 1b/2 multicenter trial designed to evaluate MVP-S combined with intermittent low dose of cyclophosphamide in patients with recurrent, epithelial ovarian, fallopian tube, or peritoneal cancer. Findings showed clinical benefit to patients with recurrent ovarian cancer, regardless of platinum sensitivity or BRCA mutational status.

DPX formulations are not limited to cancer immunotherapies. With its unique cargo carrying capacity and non-circulating lipid delivery, there is potential with DPX to develop improved mRNA vaccines, multivalent viral vaccines, vaccines for desensitizing immune response for allergies, and immune system diseases. Prior clinical studies by IMV have supported proof of concept and a superior immune response with a DPX-RSV formulation, DPX-rHA/DPX-FLU influenza vaccine, DPX-packaged survivin/MAGE-Ag for advanced metastatic bladder cancer, and certain other infectious diseases.

Through the transaction, BioVaxys has acquired 25 distinct families of patents and/or patent applications, with over one hundred related international filings related to maveropepimut-S, DPX and its use across a range of immune system-related diseases, associated trademarks, and other intellectual property. The deal also assigns to Biovaxys a royalty-bearing License and Supply Agreement with Wisconsin-based SpayVac for Wildlife Inc., on sales of animal vaccine products using technology acquired by BioVaxys, a milestone payments and royalty bearing license agreement with Pfizer animal health spin-out Zoetis Inc, the world’s largest producer of medicine and vaccinations for pets and livestock, for their development and sale of various animal health products using the technology acquired by BioVaxys, and German pharmaceuticals company Merck KGaA for survivin proteins. Survivins are highly expressed in most cancers and are associated with a poor clinical outcome, with the differential expression of survivin in cancer cells compared to normal tissues and its role as a nodal protein in a number of cellular pathways make it a significant target for cancer therapeutics.

Kenneth Kovan, BioVaxys President & Chief Operating Officer stated: "This is an absolutely transformational transaction for Biovaxys that is synergistic with our pre-existing personalized immunotherapeutic vaccines based on our HapTenix© ‘neoantigen’ tumor cell construct platform, and BVX-0918, our ovarian cancer vaccine candidate. The DPX platform and addition of maveropepimut-S to our pre-existing clinical pipeline immediately positions BioVaxys as a major player in ovarian cancer, and expands our pipeline to include advanced Relapsed-Refractory Diffuse Large B Cell Lymphoma (DLBCL), bladder and breast cancer." Kovan added, "We see tremendous commercial potential with the DPX platform, which was a major driver of the transaction. The range of antigens that can be packaged and the cargo capacity of DPX present the opportunity for BioVaxys to monetize multiple development partnerships such as in the multi-valent and mRNA vaccine fields, expand our own immunotherapeutric pipeline, and establish what we believe will be an almost perpetual string of new BioVaxys IP derived from novel DPX formulations. We envision DPX enabling new immunotherapeutics not just from BioVaxys, but from a number of other companies via business development partnerships"

James Passin, Biovaxys CEO, stated: "We are honored to continue to advance the outstanding scientific work completed by the former IMV Inc. The overwhelming support that we have received from our investors for this transaction reinforces our conviction that the antigen-packaging and presenting technology that we have acquired will position BioVaxys as a potential world leader in cancer immunotherapy with further growth potential in other significant verticals including allergy desensitization and mRNA."

It is anticipated that the transaction will fully close within ten days.

On February 12, 2024 Sana Biotechnology, Inc. (Nasdaq: SANA), a company focused on changing the possible for patients through engineered cells, reported that it has closed its underwritten upsized public offering of 21,772,728 shares of its common stock, which includes the full exercise of the underwriters’ option to purchase 4,500,000 additional shares of its common stock, at a price to the public of $5.50 per share and, in lieu of common stock to certain investors, pre-funded warrants to purchase 12,727,272 shares of its common stock at a price to the public of $5.4999 per pre-funded warrant, which represents the per share public offering price of each share of common stock less the $0.0001 per share exercise price for each pre-funded warrant (Press release, Sana Biotechnology, FEB 12, 2024, View Source [SID1234639985]). All of the shares and pre-funded warrants were sold by Sana. The gross proceeds from the offering were approximately $189.75 million before deducting underwriting discounts and commissions and other offering expenses.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Morgan Stanley, J.P. Morgan, Goldman Sachs & Co. LLC, and BofA Securities acted as joint book-running managers for the offering.

The offering was made pursuant to a Registration Statement on Form S-3, including a base prospectus, previously filed with and declared effective by the SEC. Sana has filed with the SEC the final prospectus supplement and accompanying prospectus relating to the offering. These documents can be accessed for free through the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained from: Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014 or by email at [email protected]; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; Goldman Sachs & Co. LLC, Attn: Prospectus Department, at 200 West Street, New York, NY 10282, by telephone at (866) 471-2526 or by email at [email protected]; or BofA Securities, Attn: Prospectus Department, NC1-022-02-25, 201 North Tryon Street, Charlotte, NC 28255-0001 or by email at [email protected].

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

On February 12, 2024 Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, reported an upfront cash payment and equity investment from TG Therapeutics, Inc. (Nasdaq: TGTX) for an exclusive license to develop Azercabtagene Zapreleucel (azer-cel) for autoimmune diseases, and other indications outside of cancer (Press release, Precision Biosciences, FEB 12, 2024, View Source [SID1234639984]). This is the first in a series of payments, with Precision to receive a total of $17.5 million in upfront and potential near-term payments as part of the consideration for this license.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In exchange for global rights to azer-cel for autoimmune diseases and indications outside of cancer, Precision has received an upfront payment totaling $7.5 million, consisting of cash and the purchase of 2,920,816 shares of Precision common stock by TG Therapeutics at a price of $0.77 per share, a 100% premium to the 30-day volume-weighted average price (VWAP) prior to purchase.

Precision will also receive an additional $2.5 million within 11 months, as an equity investment in Precision’s common stock at 100% premium to the then 30-day VWAP prior to purchase. Upon the achievement of certain near-term clinical milestones, Precision will also receive an additional $7.5 million payment. Precision is eligible to receive up to $288 million in milestone payments in addition to high-single-digit to low-double-digit royalties on net sales.

Precision expects that these recent payments from its azer-cel transactions, along with existing cash and cash equivalents, expected operational receipts, continued fiscal and operating discipline, and availability of Precision’s at-the-market (ATM) facility will extend Precision’s cash runway into the first half of 2026, through phase 1 clinical readouts for its wholly owned programs.

On February 12, 2024 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported the initiation of a REM-001 15-patient clinical trial (NCT05374915) in cutaneous metastatic breast cancer (CMBC) patients (Press release, Kintara Therapeutics, FEB 12, 2024, View Source [SID1234639983]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This open label 15-patient study in CMBC patients is evaluating REM-001, a second-generation photodynamic therapy (PDT) photosensitizer agent, and is designed to test the 0.8 mg dose as well as optimize the study design in advance of a Phase 3 trial initiation. The primary endpoint in the study is Best Overall Objective Response Rate (bORR) (complete response or partial response) of the target treatment fields at any time from treatment up to, and including, week 24.

In June 2023, Kintara was awarded a $2.0 million Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH) to support the clinical development of REM-001 in CMBC. This grant will cover the majority of the costs to run this clinical study.

"We are encouraged by the extensive data from prior REM-001 therapy trials supporting its strong efficacy in CMBC patients, providing us with an opportunity to address a significant unmet medical need," said Robert E. Hoffman, President and CEO of Kintara. "With an 80% complete response rate for evaluable lesions in CMBC patients observed in previous late-stage clinical trials and the support of the NIH, along with the FDA’s Fast Track Designation, we are confident in the potential of REM-001 to help CMBC patients."

"CMBC is a devastating disease with limited treatment options for patients," said Alina Markova, M.D., Section Head, General Dermatology and Oncodermatology at Memorial Sloan Kettering Cancer Center and Principal Investigator of the REM-001 15-patient study. "I am looking forward to testing the therapeutic potential of REM-001 in this trial and bringing novel therapies to CMBC patients to improve their quality of life."

Cutaneous metastases can develop with any metastatic cancer but are believed to occur most frequently in metastatic breast cancer. A 2003 meta-analysis of over 20,000 metastatic cancer patients found that 24% of the breast cancer patients included in the analysis had developed cutaneous metastases, which was the highest rate of any cancer type. Based on a 2017 analysis, the current prevalence of metastatic breast cancer in the United States is estimated to be over 168,000. Accordingly, the prevalence of CMBC may be in excess of 40,000 cases annually in the United States.