Synlogic Announces Participation in SVB Securities Healthcare Therapeutics Forum

On June 26, 2023 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company advancing novel, oral, non-systemically absorbed biotherapeutics to transform the care of serious diseases, reported that its management team will participate in the SVB Securities Healthcare Therapeutics Forum, being held in New York, July 11-12, 2023 (Press release, Synlogic, JUN 27, 2023, View Source [SID1234632935]). The Synlogic team will be available for one-on-one investor meetings. To register for the conference or request one-on-one meetings, please contact your SVB Securities representative.

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European Patent Office Grants ONK Therapeutics’ Foundational Patent for CISH Knockout in NK Cells for Use in Cancer Therapies

On June 27, 2023 ONK Therapeutics Ltd, an innovative NK cell therapy company, reported that the European Patent Office (EPO) has granted its licensed patent covering CISH knockout (KO) in NK cells, irrespective of the source of the NK cells, including human cord blood-derived, peripheral blood-derived, and NK cells derived from induced pluripotent stem cells (iPSCs) (Press release, ONK Therapeutics, JUN 27, 2023, View Source [SID1234632933]).

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The patent granted to ONK’s licensor, WEHI (Walter and Eliza Hall Institute of Medical Research), by the EPO is part of a portfolio which includes granted US, Australian, New Zealand and Japanese patents as well as pending applications in several other countries.

ONK licensed the patent family relating to the KO of CISH in NK cells in an exclusive global patent license agreement from WEHI in 2021. CISH KO has been shown to improve the persistence, metabolic profile, and cytotoxicity of NK cells. The patent granted by EPO specifically covers CISH KO NK cells per se, and cancer therapies that utilize NK cells with CISH KO as well as NK cells engineered with the foundational CISH KO in combination with IL-15 (soluble or engineered), TGFβR2 KO, or TGFβR2 KO and IL-15 (soluble or engineered).

ONK and WEHI continue to prosecute the CISH patent portfolio in a way to maximize its depth and breadth of scope. It forms part of ONK’s broad and growing IP estate covering the optimization of persistence, metabolic profile and cytotoxic potential of its NK cell therapy platform.

ONK Therapeutics’ CEO Chris Nowers said, "Editing of NK cells to knockout CISH has the potential to improve the potency and persistence of NK cell-based therapies and provide greater benefit to patients. We are actively exploring the merits of CISH KO alone or in combination with other gene edits such as TGFβR2 KO and IL-15 knock-in. We believe this is the foundational CISH KO patent, based on the earliest scientific discoveries and covers CISH KO NK cells from any source. We are excited to have this broad and evolving patent estate which underpins our scientific efforts in the field."

WEHI’s Head of Biotechnology and Commercialisation Dr Anne-Laure Puaux said, "Cell-based therapies have demonstrated their enormous potential as disease-modifying therapies in oncology. Partnerships and collaborations are key to advancing WEHI’s drug discovery and development programs, to help us take our research from the lab to the clinic. Through this license agreement with ONK Therapeutics, we are excited to support the opportunity to develop more potent cell-based therapies for the future benefit of cancer patients."

-Ends-

About CISH and the WEHI patent

CIS (encoded by the gene CISH) is a member of the suppressor of cytokine signaling (SOCS) family of proteins. When NK cells are stimulated with growth factors, such as interleukin 15 (IL-15), which encourage their growth, survival, and killing capability, there is an increase in the activity of CIS protein, which acts as a brake or checkpoint, on further NK cell growth and function.

The WEHI team found that when CIS was removed from NK cells by deleting the CISH gene, the NK cells were more responsive to growth factors and had improved survival and killing capacity(1). Later studies found that removing CIS improved the metabolic fitness of NK cells, optimizing their ability to kill tumor cells(2-3).

1. Delconte, R., Kolesnik, T., Dagley, L. et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol 17, 816–824, 2016

2. Daher et al., Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells, Blood 137(5), 624-636, 2021

3. Zhu et al., Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity, Cell Stem Cell 27(2), 224-237.e6, 2020

Nkarta Updates Clinical Progress of CAR-NK Cell Therapy NKX101 for Patients with Relapsed or Refractory Acute Myeloid Leukemia

On June 27, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported positive updated data from its Phase 1 study of NKX101 to treat patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) (Press release, Nkarta, JUN 27, 2023, View Source [SID1234632932]). NKX101 is an allogeneic, off-the-shelf cell therapy candidate comprising NK cells derived from healthy donors and engineered to target NKG2D ligands on cancer cells.

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Four of six patients in one dose expansion cohort achieved a best composite complete response (67% CR/CRi rate) after receiving at least one cycle of NKX101. In this cohort, a cycle consisted of three weekly doses of NKX101 at 1.5 billion cells per dose after treatment with fludarabine (Flu) and Ara-C (cytarabine) for lymphodepletion. Ara-C is an established and important drug in the treatment of AML across treatment lines, including first line therapy. Exposure to Ara-C is also known to upregulate NKG2D ligands, potentially increasing sensitivity of cancerous cells to NK-cell mediated killing. Data from the NKX101 study suggest Ara-C has the potential to be an effective agent for lymphodepletion.

"Patients with relapsed or refractory AML have few treatment options, and novel approaches are urgently needed. Traditional chemotherapy is often unable to drive deep remissions in this setting, and many patients cannot tolerate it," said Carlos Bachier, M.D., Medical Director of Research and Cellular Therapy, Sarah Cannon Transplant & Cellular Therapy Program at Methodist Hospital in San Antonio, Texas. "NKX101 following lymphodepletion with fludarabine and Ara-C had encouraging anti-tumor activity in a small number of patients with difficult to treat relapsed/refractory AML. This activity, together with its tolerable safety profile, merits further study of NKX101."

"NK cell therapy has long held promise for patients with AML, and these latest results highlight our continued progress towards delivering on that promise with NKX101," said David R. Shook, M.D., Nkarta’s Chief Medical Officer. "While these data are early and in a small number of patients, the response rate exceeds the rate observed with even the latest approved agents and highlights the potential advantages of lymphodepletion using Flu/Ara-C."

Nkarta expects to enroll 12 to 20 additional patients in the expansion cohort using Flu/Ara-C lymphodepletion of the Phase 1 clinical trial and provide a clinical update in the first half of 2024. Nkarta also plans to introduce protocol changes intended to standardize criteria for retreatment and consolidation and simplify study logistics for enrolled patients.

Evaluating NKX101 in r/r acute myeloid leukemia
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses donor-derived NK cells engineered to target NKG2D ligands on cancer cells. NKX101 is being evaluated in a dose-escalation Phase 1 study as a multi-dose, multi-cycle cellular therapy in patients with r/r AML. As of June 10, 2023, a total of 36 patients with r/r AML were enrolled, compared to 17 at the previous update of April 21, 2022.

Thirty patients with r/r AML were treated with NKX101 after lymphodepletion with fludarabine and cyclophosphamide (Flu/Cy), through dose finding and a separate dose expansion cohort. The majority (17/30, 57%) of patients had poor risk disease. The patients in these cohorts were heavily pre-treated, with 2 median lines of therapy (range 1-12) and 27/30 (90%) having been treated with venetoclax.

A separate, expansion cohort enrolled 6 patients who received lymphodepletion with Flu/Ara-C followed by 3 weekly doses of NKX101 at 1.5 billion cells per dose. This cohort included 5/6 (83%) patients with poor risk disease and other additional high-risk clinical features such as early relapse after allogeneic hematopoietic cell transplant (HCT) and chemo-refractory disease. The patients in this cohort were also heavily pre-treated, with 2 median lines of therapy (range 1-3) and all having been previously treated with venetoclax-containing regimens. Today’s announcement is the first time that results from the Flu/Ara-C cohort are being presented.

Safety in NKX101
NKX101 was well tolerated. No dose-limiting toxicities were observed across all cohorts. The safety profile of NKX101 was consistent across both lymphodepletion regimens. The emerging safety profile of NKX101 is positively differentiated from those of many cell therapies.

In patients with r/r AML that received lymphodepletion with Flu/Cy (Table 1), limited CAR T-like toxicities were observed, including 5 (12%) ≤grade 2 infusion reactions, 5 (12%) cases of ≤grade 2 cytokine release syndrome (CRS), 1 case of grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS), and no graft-versus-host disease (GvHD). The most common higher-grade adverse events were myelosuppression – a condition resulting in fewer red blood cells, white blood cells and platelets, as well as infection, which are common in this patient population post lymphodepletion.

Safety Table 1 – Patients treated with fludarabine / cyclophosphamide lymphodepletion

Grade 3+ AEs in ≥10% of patients Total (n=30)​​
Hematologic Events​ ​
Thrombocytopenia​ 18 (60%)​​
Anemia​ 16 (53%)
Neutropenia​ 13 (43%)​​
Febrile neutropenia ​ 8 (27%) ​
White blood cell count decreased​ 5 (17%)​
Leukocytosis​ 4 (13%)​
Infections​ ​
Pneumonia​ 3 (10%)​​
Other​ ​
Hypoxia​^​ 4 (13%)​​
Fatigue​ 3 (10%)​
Hypotension 3 (10%)

Treatment emergent adverse events regardless of relationship based on interim data from open clinical database as of 10 June 2023 ​
^ In the setting of febrile neutropenia/pneumonia

In patients with r/r AML in the expansion cohort using Flu/Ara-C lymphodepletion (Table 2), there were no observations of CRS, ICANS or GvHD of any grade. Myelosuppression and infection remained the most common higher-grade adverse events. However, there were no >grade 3 infections, and no treatment-associated fatalities.

Safety Table 2 – Patients treated with fludarabine / Ara-C lymphodepletion

Grade 3+ AEs in >1 patient Total (n=6)​​
Hematologic Events​ ​
Anemia​ 3 (50%)
Febrile neutropenia​ 3 (50%)​​
Neutropenia ​ 3 (50%) ​
Thrombocytopenia 2 (33%)
Lymphocyte count decreased​ 2 (33%)​
WBC decreased 2 (33%)​
Infections​ ​
Sepsis 3 (50%)​​

Clinical Activity in NKX101
In patients with r/r AML that received Flu/Ara-C lymphodepletion, 4 of 6 achieved CR/CRi (67% CR/CRi rate) and 3 of 6 achieved a complete response with hematologic recovery (50% CR rate). Two of the 4 reported complete responses were MRD (measurable residual disease) negative. MRD negativity is broadly viewed as an important quantitative measure of disease burden in AML and is associated with increased disease-free survival and decreased risk of recurrence. One patient with MRD positive CR underwent allogeneic HCT and remains in CR at 4 months. Another patient with CR has no detectable disease by flow cytometry and additional MRD testing is pending. Flu and Ara-C are often combined with other chemotherapies, such as idarubicin and mitoxantrone in r/r AML, and such combinations (e.g. FLAG-Ida) have been used as a part of comparator arms in multiple registrational studies, with CR rates between 10-12%.

In patients with r/r AML that received Flu/Cy lymphodepletion, and the highest doses of NKX101 (3 weekly doses at 1 billion or 1.5 billion cells per dose), 4 of 18 achieved CR/CRi (22% CR/CRi rate) and 3 of 18 achieved a complete response with hematologic recovery CR (17% CR rate). There were no CRs at the lower doses of NKX101.

Conference Call Information
Nkarta management will discuss the NKX101 results on Tuesday, June 27, at 8:00 a.m. ET. To access the live webcast, please register online on the Investors section of Nkarta’s website: View Source An archived webcast and accompanying slides will be available on the Company’s website approximately two hours after the event.

About NKX101
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy donors. It is engineered with a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. NKX101 is also engineered with a membrane-bound form of interleukin-15 (IL15) for greater persistence and activity without exogenous cytokine support. To learn more about the NKX101 clinical trial in adults with AML, please visit ClinicalTrials.gov.

About the NKX101 Trial
This Phase 1 clinical trial evaluates the safety and anti-tumor activity of NKX101 as a multi-dose, multi-cycle cellular therapy following lymphodepletion in patients with r/r AML. Patients must have received at least one prior therapy, and patients diagnosed with a disease mutation must have received a targeted therapy, where approved.

Patients in the NKX101 Phase 1 trial received either fludarabine / cyclophosphamide lymphodepletion or fludarabine /Ara-C lymphodepletion followed by NKX101. Patients received doses of 100 million, 300 million, 1 billion or 1.5 billion NK cells three times in the 3-dose regimen, or doses of 150 million or 1.5 billion NK cells two times in the 2-dose regimen. Based on tumor response and tolerability assessment, patients were eligible to receive additional treatment cycles. Disease assessment was performed by investigator review according to the ELN response criteria.

Journal of Clinical Oncology Publishes Results of Corcept’s Phase 2 Trial of Relacorilant in Women With Platinum-Resistant Ovarian Cancer

On June 27, 2023 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrine, oncologic, metabolic and neurological disorders by modulating the effects of the hormone cortisol, reported publication of the final analysis from its Phase 2 trial evaluating its proprietary cortisol modulator, relacorilant, in women with platinum-resistant ovarian cancer in the Journal of Clinical Oncology (JCO), the premiere journal of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Corcept Therapeutics, JUN 27, 2023, https://ir.corcept.com/news-releases/news-release-details/journal-clinical-oncology-publishes-results-corcepts-phase-2 [SID1234632930]).

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The publication is titled Relacorilant + Nab-Paclitaxel in Patients with Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study and can be accessed at the following link: View Source

In the trial, patients who received relacorilant orally the day before, the day of and the day after their nab-paclitaxel infusion ("intermittent dosing") experienced a 34 percent reduction in risk of disease progression (median PFS=5.6 vs. 3.8 months, HR 0.66, P=0.038), responded to treatment longer (median DoR=5.6 vs. 3.7 months, HR 0.36, P=0.006) and had a 33 percent reduction in risk of death (median OS=13.9 vs. 12.2 months, HR 0.67, P=0.066) compared to patients who received nab-paclitaxel alone. Adverse events were comparable across the study arms.

PFS and OS benefits were exhibited across multiple subgroups of patients. Patients who would have met the eligibility requirements for Corcept’s confirmatory Phase 3 ROSELLA trial did especially well. A post-hoc analysis showed that patients who had received prior bevacizumab, did not have primary platinum-refractory disease and who had received no more than three prior lines of therapy experienced a 62 percent reduction in risk of death (median OS=17.9 vs. 12.6 months, HR 0.38, P=0.011) compared to similar patients who received nab-paclitaxel alone.

"Outcomes for patients with platinum-resistant ovarian cancer are poor and treatment options are limited," said first author of the publication Nicoletta Colombo, MD, PhD, Associate Professor, Obstetrics and Gynecology, University of Milan-Bicocca, Director, Ovarian Cancer Center, and Chair, Program of Gynecology, European Institute of Oncology, IRCCS, Milan Italy. "The benefits experienced by patients in the intermittent dosing group are meaningful especially given the simple, oral dosing and favorable safety profile of relacorilant. We are on the cusp of developing an entirely new way to treat this serious disease."

"We are excited by the data from our Phase 2 trial and enthusiastic the results have been published in the Journal of Clinical Oncology. Our single goal is to replicate the great results seen in our phase 2 trial," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "We believe relacorilant has the potential to become a new standard of care for all patients with platinum-resistant ovarian cancer."

About Platinum-Resistant Ovarian Cancer

Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns less than six months after receiving platinum-containing therapy are described as having "platinum-resistant" disease. In the United States, approximately 20,000 women with platinum-resistant disease are candidates to start a new therapy each year. There are few treatment options and median overall survival following recurrence of disease is typically 12 months or less with single-agent chemotherapy.

Coherus BioSciences Announces New Employment Inducement Grants

On June 26, 2023 Coherus BioSciences, Inc. ("Coherus" or the "Company", Nasdaq: CHRS), reported that effective June 20, 2023, the compensation committee of the Company’s board of directors granted options to purchase an aggregate of 48,000 shares of the common stock of the Company to six newly hired employees with a per share exercise price of $3.84, the closing trading price on the grant date (Press release, Coherus Biosciences, JUN 27, 2023, View Source [SID1234632929]).

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The stock options were granted pursuant to the Coherus BioSciences, Inc. 2016 Employment Commencement Incentive Plan, which was approved by the Company’s board of directors in June 2016 under Rule 5635(c)(4) of the Nasdaq Global Select Market for equity grants to induce new employees to enter into employment with the Company.