On October 3, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported an update on its ongoing Phase 1/2 clinical trial evaluating KVA12123 in patients with advanced solid tumors (Press release, Kineta, OCT 3, 2023, View Source;utm_medium=rss&utm_campaign=kineta-announces-positive-kva12123-monotherapy-safety-and-biomarker-data-from-its-ongoing-phase-1-2-vista-101-clinical-trial [SID1234635598]). KVA12123, Kineta’s immuno-oncology drug targeting VISTA, cleared the first three monotherapy dose levels and was well tolerated with no dose limiting toxicities (DLT) or cytokine related adverse events observed. Additionally, KVA12123 exhibited a greater than dose-proportional pharmacokinetic profile achieving greater than 90% VISTA receptor occupancy (RO) across patients in the 30 mg dosing cohort.

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"We are very pleased with the progress of our Phase 1/2 clinical trial, showing very compelling initial safety and pharmacokinetic data for KVA12123, which we believe significantly de-risks VISTA as a novel drug target," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "We appreciate the patients and healthcare providers that are participating in this important study, and we look forward to further evaluating KVA12123’s potential for treating patients with advanced solid tumors."

The VISTA-101 trial (NCT05708950) enrolled 11 patients with advanced solid tumors in the first three monotherapy dose-escalation cohorts, where subjects received either 3, 10 or 30 mg of KVA12123 by intravenous (IV) infusion every two weeks. Primary objectives of the Phase 1/2 study are to evaluate the safety and tolerability of KVA12123 and to determine the recommended Phase 2 dose (RP2D). Patients enrolled in the study were heavily pretreated with multiple prior lines of therapy including chemotherapy, radiation, and immunotherapy.

Safety Profile
In the first three monotherapy cohorts, KVA12123 was well tolerated at all doses and no DLTs were observed. Furthermore, as KVA12123 was engineered to mitigate adverse events associated with cytokine release syndrome (CRS), the study is closely monitoring proinflammatory cytokines that are associated with CRS (IL-6 and TNFα) in the Phase 1 portion of the study. No evidence of CRS or proinflammatory cytokine induction have been observed at any dose level with KVA12123 in the initial cohorts.

Pharmacokinetics and Receptor Occupancy
To guide the RP2D decision, Kineta developed a proprietary assay to evaluate VISTA RO on immune cells from patients treated with KVA12123. Greater than 90% VISTA RO was achieved at the 30 mg dose. Furthermore, pharmacokinetic analyses demonstrated a greater than dose-proportional increase in drug exposure across all evaluated doses, consistent with target-mediated drug disposition at lower doses.

"We are thrilled to see greater than 90% VISTA receptor occupancy in patients treated with 30 mg dose. This indicates that we can saturate the target without dose limiting toxicities and are close to achieving an optimal dose for KVA12123," said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. "We believe that KVA12123 has the potential to become an important new immunotherapy for the many patients with cancer in need of new therapeutic options."

Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of CRS in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 effectively de-risks the VISTA target and provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer.

The company will continue escalating monotherapy dose cohorts of KVA12123 in Part A and initiate Part B of the study to evaluate KVA12123 in combination with pembrolizumab. Initial monotherapy efficacy data are anticipated in Q4 2023 and will be presented, along with safety data, at an upcoming medical conference.

On October 3, 2023 Invitae (NYSE: NVTA), a leading medical genetics company, reported it gained FDA market authorization for its Common Hereditary Cancers Panel (Press release, Invitae, OCT 3, 2023, View Source [SID1234635597]). This represents the first broad panel that is used to identify germline variants associated with hereditary cancer to gain market authorization from the FDA. The company believes that this is a strong vote of confidence in its Common Hereditary Cancers Panel, which has the potential to benefit patients, providers and payers.

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Through this application, Invitae was able to establish a new category of device based on its testing technology and methodology which provides potential marketing differentiation and opportunities for its largest testing category. In 2021, the company submitted a de novo application using the Common Hereditary Cancers Panel as an example of a methods-based approach to validation. The FDA worked closely with Invitae to review the test and its supporting data, which led to this authorization being granted on September 29, 2023.

"This is incredibly exciting news for Invitae. We were able to demonstrate that the way the technology works can be well characterized based on variant type and genomic context and is consistent across genes," said Robert Nussbaum, M.D., chief medical officer at Invitae. "The fact that we were able to do this is a testament to Invitae’s quality and rigorous validation process that met the agency’s standards."

About the Common Hereditary Cancers Panel

The Invitae Common Hereditary Cancers Panel is an in vitro diagnostic test focused on 47 genes already known to contain tens of thousands of genetic variants that increase risk of developing certain cancers. Hereditary cancer testing represents the largest business line of Invitae’s testing portfolio, and multiple peer-reviewed studies1 published in recent years have demonstrated its clinical utility. That utility includes determining the potential risk for cancer, informing management and treatment of those with the disease and helping to prevent disease in those at increased risk. To learn more, visit our website.

Intended Use of the Market Authorization

The Invitae Common Hereditary Cancers Panel is a qualitative high throughput sequencing-based in vitro diagnostic test system intended for analysis of germline human genomic DNA extracted from whole blood for detection of substitutions, small insertion and deletion alterations and copy number variants (CNV) in a panel of targeted genes. This test system is intended to provide information for use by qualified health care professionals in accordance with professional guidelines, for hereditary cancer predisposition assessment and to aid in identifying hereditary genetic variants potentially associated with a diagnosed cancer. The test is not intended for cancer screening or prenatal testing. Results are intended to be interpreted within the context of additional laboratory results, family history and clinical findings. The test is a single-site assay performed at Invitae Corporation.

On October 3, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN) and Intellia Therapeutics, Inc. (NASDAQ:NTLA) reported an expanded research collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases (Press release, Intellia, OCT 3, 2023, View Source [SID1234635596]). This builds on the success of the companies’ existing collaboration and continues to combine both companies’ deep biology and technology expertise. The collaboration will leverage Regeneron’s proprietary antibody-targeted adeno-associated virus (AAV) vectors and delivery systems and Intellia’s proprietary Nme2 CRISPR/Cas9 (Nme2Cas9) systems adapted for viral vector delivery and designed to precisely modify a target gene.

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"To date, the widespread use of genetic medicines has generally been limited by the inability to deliver a genetic payload to cells of interest in the body beyond the liver. This expansion of our longstanding and productive collaboration with Intellia is taking advantage of new technology and innovations to unlock these opportunities," said Aris Baras, M.D., Senior Vice President and Co-Head of Regeneron Genetic Medicines.

"Regeneron has invented and preclinically validated a proprietary antibody-directed AAV approach that builds on our decades of experience in antibodies and newly developed AAV capsid engineering technologies to deliver innovative payloads across many targeted tissue types and disease settings. We’re excited to put this approach to the test in combination with Intellia’s industry-leading gene editing systems, in hopes of generating important new medicines for people with serious neurological and muscular diseases," said Christos Kyratsous, Ph.D., Senior Vice President, Research, and Co-Head of Regeneron Genetic Medicines.

"We are excited to expand our successful collaboration with Regeneron to now accelerate the development of CRISPR-based therapies outside of the liver for the treatment of neurological and muscular diseases with significant unmet need," said Intellia President and Chief Executive Officer John Leonard, M.D. "At Intellia, we are continuously innovating our editing and delivery solutions to realize the full potential of CRISPR gene editing as a new therapeutic modality. This collaboration is representative of our long-standing belief that the most groundbreaking solutions will come from selecting the best tools for each individual application, all of which are enabled by our industry-leading genome editing toolbox."

Under the terms of the expanded agreement, the companies will initially research two in vivo non-liver targets. Intellia will lead the design of the editing methodology and Regeneron will lead the design of the targeted viral vector delivery approach. Each company will have the opportunity to lead potential development and commercialization of product candidates for one target, and the company that is not leading development and commercialization will have the option to enter into a co-development and co-commercialization agreement for the target.

On October 3, 2023 Immix Biopharma, Inc. ("ImmixBio", "Company", "We" or "Us"), reported presentation of additional AL Amyloidosis clinical data from its Phase 1b/2a NEXICART-1 (NCT04720313) study of novel, autologous, BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy, NXC-201, at an oral presentation at the 20th International Myeloma Society Annual (IMS) Meeting being held in Athens, Greece on September 27-30 2023 (Press release, Immix Biopharma, OCT 3, 2023, View Source [SID1234635595]). One new patient and additional follow-up data from an additional 8 patients (9 total) are included in this update. All patients were DARZALEX (daratumumab) combination therapy relapsed/refractory and experienced a median of 6 earlier treatments that failed to stop worsening of disease (lines of therapy) prior to receiving NXC-201.

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"There are no approved drugs for relapsed/refractory AL Amyloidosis," said Polina Stepensky, M.D., Director of the Hadassah Medical Organization’s Department of Bone Marrow Transplantation and Immunotherapy for Adults and Children, and principal study investigator. "NXC-201’s 100% response rate in relapsed/refractory AL amyloidosis patients, including t(11;14) and cardiac involved, indicates a potential broad mechanism of action. Additionally, as a one-time treatment, NXC-201 would present an attractive alternative to multi-drug combination, long-term daily or weekly regimens for relapsed/refractory AL amyloidosis patients."

"Currently, AL Amyloidosis treatment involves repeat dosing and weekly distant travel to academic medical centers," said Ilya Rachman, M.D., Ph.D., Chief Executive Officer of Immix Biopharma. "One-time treatment with NXC-201 could fill the void for relapsed/refractory AL Amyloidosis, where there are no therapies approved today, while restoring quality of life."

Gabriel Morris, Chief Financial Officer of Immix Biopharma, added, "NXC-201’s uniquely favorable CAR-T tolerability profile and an apparent ability to clear disease-causing amyloid chains from the body within ~30 days could make it particularly suitable for treatment in a potential outpatient setting."

Data were presented from 9 relapsed/refractory AL amyloidosis patients (including one new patient) in the ongoing Phase 1b/2a NEXICART-1 study of NXC-201 (formerly HBI0101). Patients were infused with CAR+T cells at doses of 150 x 106 (n=1), 450 x 106 (n=2), and 800 x 106 (n=6).
Of the 9 patients, 7/9 patients had cardiac involvement and 4/9 patients were t(11;14) relapsed/refractory. Median follow-up was 7.3 months (range: 2.5 – 16.5 months) as of the September 20, 2023 data cutoff. Data highlights:

9 relapsed/refractory AL amyloidosis patients (median 6 lines of prior therapy):

Overall response rate of 100% (9/9)
Complete response rate of 67% (6/9) (MRD 10-5)
Organ response rate of 56% (5/9)
Best responder had a duration of response of 19.2 months as of the data cutoff of September 20, 2023, with response ongoing
There were no immune effector cell-associated neurotoxicity syndrome (ICANS) events or grade 4 cytokine release syndrome (CRS) events reported
44% (4/9) had MAYO-stage IIIa/IIIb disease
For the 7 relapsed/refractory AL Amyloidosis patients with cardiac involvement:

Overall response rate of 100% (7/7)
Complete response rate of 57% (4/7) (MRD 10-5)
Organ response rate of 57% (4/7)
4 patients with t(11;14) relapsed/refractory AL Amyloidosis:

Overall response rate of 100% (4/4)
Complete response rate of 75% (3/4) (MRD 10-5)
Organ response rate of 50% (2/4)
The 20th IMS AL Amyloidosis presentation can be accessed on the ImmixBio corporate website at this link: View Source
Oral Presentation:

Event 20th International Myeloma Society Annual Meeting, Athens, Greece
Title "Feasibility of a novel academic anti-BCMA chimeric antigen receptor T-cell (CART) (HBI0101) for the treatment of relapsed and refractory AL amyloidosis"
Presentation
Date/Time (EEST)
September 27, 2023 9:00am – 14:30pm;
September 28, 2023 10:00 – 13:30pm;
September 29, 2023 9:30 – 14:15pm
About NEXICART-1

NEXICART-1 (NCT04720313) is an ongoing Phase 1b/2a, open-label study evaluating the safety and efficacy of NXC-201 (formerly HBI0101), in adults with relapsed or refractory multiple myeloma and AL amyloidosis.

The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose (RP2D) and Phase 2 dose of NXC-201. The Phase 2 portion of the study will evaluate the efficacy and safety of NXC-201 with endpoints of overall survival, progression-free survival and response rates, according to International Myeloma Working Group (IMWG) Uniform Response Criteria.

The Phase 1b portion of the ongoing Phase 1b/2a clinical trial has been successful in determining the recommended Phase 2 dose (RP2D) of 800 million CAR+T cells. The expected primary endpoint for the Phase 2 portion of the ongoing Phase 1b/2a clinical trial of NXC-201 in relapsed/refractory multiple myeloma is overall response rate and duration of response. ImmixBio subsidiary Nexcella plans to submit data to the FDA in multiple myeloma once 100 patients are treated with NXC-201. The expected primary endpoint for NXC-201 in relapsed/refractory AL Amyloidosis is overall response rate. ImmixBio subsidiary Nexcella plans to submit data to the FDA in AL amyloidosis once 30-40 patients are treated with NXC-201.

About NXC-201

NXC-201 (formerly HBI0101) is a BCMA-targeted investigational chimeric antigen receptor T (CAR-T) cell therapy that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and AL amyloidosis.

About AL Amyloidosis

AL amyloidosis is a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. Misfolded amyloid proteins produced by plasma cells buildup in and around tissues, nerves and organs, gradually affecting their function. This can cause progressive and widespread organ damage, and high mortality rates.

AL amyloidosis affects roughly 30,000 – 40,000 patients in total throughout the U.S. and Europe, and it is estimated that there are approximately 3,000 – 4,000 new cases of AL amyloidosis annually in the U.S. The annual global incidence of AL Amyloidosis is ~15,000 patients.

The Amyloidosis market was $3.6 billion in 2017, expected to reach $6 billion in 2025, according to Grand View Research.

On October 3, 2023 Eli Lilly and Company (NYSE: LLY) and POINT Biopharma Global, Inc. (NASDAQ: PNT) reported a definitive agreement for Lilly to acquire POINT, a radiopharmaceutical company with a pipeline of clinical and preclinical-stage radioligand therapies in development for the treatment of cancer (Press release, Eli Lilly, OCT 3, 2023, View Source [SID1234635594]). Radioligand therapy can enable the precise targeting of cancer by linking a radioisotope to a targeting molecule that delivers radiation directly to cancer cells, enabling significant anti-tumor efficacy while limiting the impact to healthy tissue.

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POINT’s lead programs are in late-phase development. PNT20021 is a prostate-specific membrane antigen (PSMA) targeted radioligand therapy in development for patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on hormonal treatment. Topline data from this study are expected in the fourth quarter of 2023. PNT20031 is a somatostatin receptor (SSTR) targeted radioligand therapy in development for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Beyond the late-stage clinical pipeline, POINT has several additional programs in earlier stages of clinical and preclinical development. Additionally, POINT operates a 180,000-square-foot radiopharmaceutical manufacturing campus in Indianapolis, as well as a radiopharmaceutical research and development center in Toronto. These facilities will be utilized alongside POINT’s extensive network of supply chain partners for sourcing radioisotopes and their precursors.

"Over the past few years, we have seen how well-designed radiopharmaceuticals can demonstrate meaningful results for patients with cancer and rapidly integrate into standards of care, yet the field remains in the early days of the impact it may ultimately deliver," said Jacob Van Naarden, President of Loxo@Lilly, the oncology unit of Eli Lilly and Company. "We are excited by the potential of this emerging modality and see the acquisition of POINT as the beginning of our investment in developing multiple meaningful radioligand medicines for hard-to-treat cancers, as we have done in small molecule and biologic oncology drug discovery and development. We look forward to welcoming POINT colleagues to Lilly and working together to build upon their achievements as we develop a pipeline of meaningful new radioligand treatments for patients."

Joe McCann, Ph.D., CEO of POINT added: "The combination of POINT’s team, infrastructure and capabilities with Lilly’s global resources and experience could significantly accelerate the discovery, development and global access to radiopharmaceuticals. I look forward to a future where patients all over the world can benefit from the new cancer treatment options made possible by the joining of our two companies today."

Terms of the Agreement

Lilly will commence a tender offer to acquire all outstanding shares of POINT for a purchase price of $12.50 per share in cash (an aggregate of approximately $1.4 billion) payable at closing. The transaction has been approved by the boards of directors of both companies.

The transaction is not subject to any financing condition and is expected to close near the end of 2023, subject to customary closing conditions, including the tender of a majority of the outstanding shares of POINT’s common stock, and license transfer approval from the U.S. Nuclear Regulatory Commission. Following the successful closing of the tender offer, Lilly will acquire any shares of POINT that are not tendered in the tender offer through a second-step merger at the same consideration as paid in the tender offer.

The purchase price payable at closing represents a premium of approximately 87% to POINT’s closing stock price on Oct. 2, 2023, the last trading day before the announcement of the transaction, and 68% to the 30-day volume-weighted average price. POINT’s board of directors unanimously recommends that POINT’s stockholders tender their shares in the tender offer.

Lilly will determine the accounting treatment of this transaction as a business combination or an asset acquisition, including any related acquired in-process research and development charges, according to Generally Accepted Accounting Principles (GAAP) upon closing. This transaction will thereafter be reflected in Lilly’s financial results and financial guidance.

For Lilly, Goldman Sachs & Co. LLC is acting as exclusive financial advisor and Kirkland & Ellis LLP is acting as legal counsel. For POINT, Centerview Partners LLC is acting as exclusive financial advisor and Skadden, Arps, Slate, Meagher & Flom LLP is acting as legal counsel.