On January 18, 2022 Celularity Inc. (Nasdaq: CELU) ("Celularity"), a clinical-stage biotechnology company developing placental-derived off-the-shelf allogeneic cell therapies, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for its genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-101, which is being developed in combination with standard chemotherapy, trastuzumab and pembrolizumab in patients in first-line locally advanced unresectable or metastatic HER2/neu positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (Press release, Celularity, JAN 18, 2022, View Source [SID1234605527]). CYNK-101 is an investigational genetically modified NK cell therapy designed to synergize with approved antibody therapeutics through enhanced antibody-dependent cellular cytotoxicity (ADCC).

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Robert Hariri, M.D., Ph.D., Founder, Chairperson and Chief Executive Officer of Celularity, said, "We are extremely excited to receive this fast track designation and the support from the FDA for our investigational genetically modified NK cell therapy in the first-line setting of G/GEJ cancers. CYNK-101 is built on the foundation of our unique placental-derived source material, which as compared to other cell sources, has naturally enhanced proliferative potential (or "stemness"), that has been shown to be a determinant of persistence and efficacy potential. Using novel genetic engineering, we have enhanced the ability of CYNK-101 cells to synergize with approved antibodies and provide a novel and potentially non-cross resistant therapy to improve the lives of patients with G/GEJ cancers as well as a broad range of other indications."

"The addition of immune-based therapy of blocking PD-1 with a checkpoint inhibitor (pembrolizumab) to the prior standard of care (chemotherapy and traztuzumab) has recently been shown to be of benefit in patients with first-line HER2/neu positive unresectable G/GEJ cancer," added Andrew Pecora, M.D., President of Celularity. While overall response rates in first-line G/GEJ treated with the triple combination of chemotherapy, traztuzumab and pembrolizumab were significantly greater with the addition of pembrolizumab (74.4% vs 51.9%; p=0.000006; Keynote-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer; Janjigian Y et al., Nature 600, 727-730 (2021), complete response rates remained modest, however (11.3%). "Our recently accepted IND enables the assessment to possibly further improve outcomes in G/GEJ treated with triple combination therapy by adding CYNK-101 cells, a potentially non-cross resistant therapy (enhanced ADCC, direct NK cell tumor killing and help of T cell function and memory) after initially cytoreducing the tumor mass and potentially diminishing resistance in the tumor microenvironment with combined chemotherapy, traztuzumab and pembrolizumab "induction" followed by reinduction and maintenance with CYNK-101 cells in combination with traztuzumab and pembrolizumab."

About Fast Track Designation

Fast Track Designation is an FDA process designed to facilitate the development and expedite the review of new drugs that are intended to treat a serious condition and have the potential to address unmet medical needs. The purpose of Fast Track designation is to expedite the process of getting important new drugs to patients. The designation may offer frequent interactions with the FDA review team on the product’s development and the product may be eligible for rolling review and priority review if certain criteria are met.

About Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide(1). Despite recent improvements in treatment quality and options, advanced gastric cancer remains one of the hardest to cure cancers, with a median overall survival (OS) of 10–12 months and a five-year OS of approximately 5–20%. In May 2021, the U.S. FDA granted accelerated approval to pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2+ G/GEJ cancers (2)

REFERENCES

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68 (6):394–424. doi:10.3322/caac.21492.
FDA grants accelerated approval to pembrolizumab for HER2-positive gastric cancer. Access here: View Source Accessed January 17, 2022.
About CYNK-001

Celularity’s lead therapeutic program based on its placental-derived unmodified NK cell type is CYNK-001, an allogeneic unmodified NK cell being developed as a treatment for hematologic malignancies, solid tumors, and infectious diseases. CYNK-001 is a cryopreserved allogeneic off-the-shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells. The safety and efficacy of CYNK-001 have not been established, and CYNK-001 has not been approved for any use by the U.S. Food and Drug Administration or any other analogous regulatory authority.

On January 18, 2022 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported the appointment of Syed Rizvi, M.D., to the newly created position of chief medical officer (Press release, Caribou Biosciences, JAN 18, 2022, View Source [SID1234605526]). Dr. Rizvi has more than two decades of experience in all stages of drug development, from clinical strategy and execution through regulatory submissions to support approval and commercialization of several cancer treatments, including two autologous CAR-T cell therapies ABECMA and BREYANZI.

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"Syed’s extensive industry knowledge, strategic insight, and significant leadership experience in the development of oncology cell therapies will be valuable to Caribou as we advance our pipeline of sophisticated genome-edited allogeneic therapeutics," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "In 2022, we plan to disclose initial data from our ANTLER Phase 1 clinical trial evaluating CB-010, file an IND application for our second CAR-T cell product candidate, CB-011, and announce target selection for our first CAR-NK cell therapy, CB-020. We have a transformative year ahead of us and I am delighted to welcome Syed to the Caribou team."

"I am thrilled to join Caribou, a pioneering company at the cutting edge of CRISPR genome editing and allogeneic cell therapy discovery and development," said Dr. Rizvi. "Caribou’s promising pipeline and highly specific Cas12a chRDNA technology have the potential to revolutionize the treatment of patients with cancer and may have broader applications. I am excited to lead Caribou’s clinical development initiatives and look forward to working with our experienced leadership team, dedicated colleagues, investigators, and regulatory authorities to achieve Caribou’s mission to provide innovative, transformative therapies for patients with devastating diseases."

Dr. Rizvi most recently served as chief medical officer of Chimeric Therapeutics, where he led the strategy and execution of clinical development programs for the company’s T cell and NK cell therapy platforms and helped build the pipeline. Previously, he worked for Legend Biotech, a cell therapy company, serving as head and vice president of clinical development, clinical operations, safety, data sciences, project management, and medical affairs, and he served as co-chair of the joint development committee for the Legend-Janssen collaboration. At Legend, he led the development of Cilta-cel, an autologous BCMA CAR-T cell therapy, as well as other cell therapies. Earlier, he worked for Celgene Corporation (now a Bristol Myers Squibb Company), serving as the head of global medical affairs for CAR-T cell programs and head of hematology and immuno-oncology for U.S. medical affairs. At Celgene, he was responsible for the strategic direction and management of Celgene’s CAR-T cell and immuno-oncology therapy portfolios. He built a comprehensive clinical research alliance and developed an immuno-oncology network with researchers to harness scientific learnings and advance clinical development for targeted patient outcomes. At Celgene, he was responsible for the global medical strategy supporting the clinical development of ABECMA in multiple myeloma and BREYANZI in lymphoma, both autologous CAR-T cell therapies. He previously held global clinical leadership positions of increasing responsibility for oncology programs at Novartis, Merck, and Genta, Inc.

Dr. Rizvi received his medical degree from Dow Medical College and spent several years in direct patient care before joining Saint Vincent’s Comprehensive Cancer Center in New York. Dr. Rizvi has authored numerous peer-reviewed publications and is a member of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the American Society of Hematology (ASH) (Free ASH Whitepaper), the American Society for Transplantation and Cellular Therapy, and other professional organizations.

About Caribou’s Novel Next-Generation CRISPR Platform

CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Type II CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems occasionally edit unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed chRDNAs (pronounced "chardonnays"), RNA-DNA hybrid guides that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On January 18, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported new data from its lead clinical program evaluating onvansertib in combination with standard-of-care (SOC) FOLFIRI/bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, JAN 18, 2022, View Source [SID1234605525]). A subset of these data will be featured in a poster presented by Dr. Heinz-Josef Lenz, principal investigator, USC Norris Comprehensive Cancer Center, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCOGI) on Saturday, January 22, 2022.

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"As we have increased the number of patients evaluated and the duration of follow-up, our Phase 1b/2 trial has consistently generated data suggesting that onvansertib provides meaningful clinical benefits when added to SOC," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "The objective response rate and median progression free survival observed substantially exceed what would be expected with SOC alone, and five patients receiving onvansertib have been able to pursue potentially curative metastasis-directed treatments. We also observed a confirmed complete response, which is exciting given the difficult-to-treat nature of second line mCRC patients."

The most current data for the trial are shown below and include patient follow up collected after the cutoff dates for both the ASCO (Free ASCO Whitepaper)-GI abstract and poster (one additional PR was recorded after December 3):

Efficacy data in evaluable patients (represents an update from ASCO (Free ASCO Whitepaper)-GI abstract/poster):
•Among patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) in combination with FOLFIRI-bev:
◦12 of 35 (34%) achieved an initial complete response (CR) or partial response (PR)
◦10 of 35 (29%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
◦33 of 35 (94%) had a best response of disease control (CR + PR + SD)
◦Objective response rates of 5-13% observed in historical control trials in similar patient populations treated with various different drug combinations, including the standard of care chemotherapy of FOLFIRI with bevacizumab1-4
•Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2)
◦17 of 48 (35%) achieved an initial CR or PR
◦13 of 48 (27%) have achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
◦44 of 48 (92%) had a best response of disease control (CR + PR + SD)
•Status of 4 unconfirmed PRs:
◦1 patient discontinued from the trial prior to confirmatory scan due to an adverse event that was unrelated to treatment (hepatitis B)
◦1 patient went from PR to SD at the confirmatory scan and patient subsequently discontinued from the trial to pursue potentially curative metastasis-directed therapy
◦1 patient went from PR to SD at the confirmatory scan (patient remains on treatment)
◦1 patient has yet to have their confirmatory scan
•5 of 48 (10%) evaluable patients discontinued therapy to pursue potentially curative metastasis- directed therapy (surgery or microwave ablation), including 2 patients with SD

Median progression free survival (mPFS; no update from ASCO (Free ASCO Whitepaper)-GI poster)
•mPFS has not yet been reached in patients treated per protocol at the RP2D
•mPFS across all response-evaluable patients (n = 48) is 9.4 months (95% confidence interval: 7.1 – not yet reached)
•mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4

Biomarker data across all patients (no update from ASCO (Free ASCO Whitepaper)-GI poster):
•Responses (CRs or PRs) were observed across seven different KRAS mutation variants, including the 3 most commonly observed in colorectal cancer (G12D, G12V, G13D)
•Patients achieving a best response of a CR or PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) measured by droplet digital PCR (ddPCR) after 1 cycle (28 days) of therapy

Safety data across all patients (no update from ASCO (Free ASCO Whitepaper)-GI poster):
•The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 11% (84/788) of reported treatment-emergent adverse events (TEAEs) being G3/G4
◦The most commonly reported adverse event was neutropenia/neutrophil count decreased
◦Most reported TEAEs were manageable and reversible with supportive care

Baseline characteristics of patients at all dose levels (no update from ASCO (Free ASCO Whitepaper)-GI poster):

•The patients’ median age was 61 years (range 35-83), and 56% were male
•67% patients had previously received bevacizumab
•16 of 48 (33%) evaluable patients remain on trial at the data cutoff date

Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "These impressive results show radiographic responses across multiple KRAS mutation variants when onvansertib is combined with the standard of care regimen of FOLFIRI-bev and demonstrate a substantial increase in disease response relative to historical controls. We believe the data presented today further validate the potential of onvansertib to provide a meaningful improvement in the treatment outcome of a large patient population that has limited available treatment options. Looking forward, and with our strong cash position, we have the ability to explore the full potential of onvansertib."

Webcast and Conference Call
The newly announced data are being discussed today at 5:00 PM ET as part of a webcast and conference call with members of the Cardiff Oncology management team. To access the webcast, click here. To participate by phone, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13725845. Following the live event, an archived webcast will be available on the "Events" section of the Cardiff Oncology website.

About the Phase 1b/2 Trial of Onvansertib in the Second-Line Treatment of KRAS-mutated mCRC This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation.
Patients must also have experienced disease progression or treatment intolerance to first-line treatment with fluoropyrimidine and oxaliplatin (FOLFOX or CapeOx) with or without bevacizumab to be eligible.
The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit NCT03829410.

References
1.Giessen et al., Acta Oncologica 2015, 54: 187-193
2.Cremolini et al., Lancet Oncol 2020, 21: 497–507
3.Antoniotti et al., Correspondence Lancet Oncol June 2020
4.Bennouna et al., Lancet Oncol 2013; 14: 29–37

On January 18, 2022 BioLineRx Ltd. (NASDAQ-CM: BLRX) (TASE: BLRX) a late clinical-stage biopharmaceutical company focused on oncology, reported that the Company has completed a successful pre-New Drug Application (NDA) meeting with the US Food and Drug Administration (FDA) regarding Motixafortide as a novel stem-cell mobilization agent for autologous bone marrow transplantation in multiple myeloma patients (Press release, BioLineRx, JAN 18, 2022, View Source [SID1234605524]).

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The purpose of the meeting was to obtain agreement from the FDA on the content of the proposed NDA and, in particular, to confirm that the Company’s single Phase 3 pivotal study, GENESIS, is sufficient to support an NDA submission. During the pre-NDA meeting, the FDA agreed that the proposed data package is sufficient to support an NDA submission, which the Company continues to anticipate will occur in H1 2022.

"We are highly encouraged by the collaborative pre-NDA meeting that we held with the FDA, and having confirmed alignment with the agency, our NDA submission remains on track for the first half of this year," stated Philip Serlin, Chief Executive Officer of BioLineRx. "This successful meeting continues the positive momentum generated from the compelling results of our GENESIS Phase 3 study, which demonstrate a highly significant improvement over the current standard of care, alongside the positive results of the pharmacoeconomic study that we reported more recently. As a result, Motixafortide, if approved, has the potential to become the standard-of-care mobilization therapy for all multiple myeloma patients undergoing autologous stem cell transplantation, especially in light of new and more intense induction treatment regimens given to these patients, which make stem-cell mobilization more difficult than ever before," concluded Mr. Serlin.

In May 2021, BioLineRx announced positive top-line results from its GENESIS Phase 3 trial of Motixafortide in stem-cell mobilization for autologous bone marrow transplantation in multiple myeloma patients. The study met all primary and secondary endpoints with a very high degree of statistical significance (p<0.0001). Importantly, ~90% of patients went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of Motixafortide and in only one apheresis session.

On January 18, 2022 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported the national launch of its new GeneStrat NGS genomic test, a blood-based tumor profiling test (Press release, Biodesix, JAN 18, 2022, View Source [SID1234605523]). The 52-gene panel includes guideline recommended mutations to help physicians treating advanced- stage lung cancer patients identify targeted therapy mutations, such as EGFR, ALK, KRAS, MET, NTRK, ERBB2, and others, and delivers them in an expedited timeframe so patient treatment can begin sooner.

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The GeneStrat NGS test is paired with advanced variant interpretation technology connected to a powerful knowledge database developed by PierianDx. Physicians will now receive a streamlined report, including genomic insights for more precise patient care in an unprecedented 72-hour turnaround time.

The GeneStrat NGS test is paid by Medicare under the National Coverage Determination (NCD) for NGS Manual 90.2 section D by Novitas Solutions.

The Company also announced the launch of its new IQLung Treatment Guidance Testing Strategy, which includes the new GeneStrat NGS and a broader view of each patient’s disease state. The testing strategy also includes blood-based proteomic and genomic testing workflows for both early and advanced stage lung cancer that can aid physicians in making treatment decisions. Biodesix plans to add additional tests in development to their IQLung portfolio.

"Initiating treatment as early as possible can help improve patient outcomes," said Scott Hutton, CEO, Biodesix. "Studies show the length of time to receive tests results impacts how quickly a patient goes on treatment. Current NGS tests can take anywhere from a week to a month to return results. This delay of diagnostic information contributes to patient anxiety and compliance, further delaying treatment when time is imperative in fighting lung cancer. It is our mission to change this paradigm, and we offer tests that provide important results in three days so patients can begin treatment as swiftly as possible."