On December 13, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, reported that positive clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT516 for patients with relapsed / refractory B-cell lymphoma (BCL) at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Fate Therapeutics, DEC 13, 2021, View Source [SID1234596919]). FT516 is the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells.

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In addition, the Company reported that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to FT516 for the treatment of relapsed / refractory diffuse large B-cell lymphoma (DLBCL). The RMAT program provides all of the benefits of the fast track and breakthrough therapy designation programs such as early interactions with the FDA to discuss potential pathways for accelerated approval.

"We continue to be highly encouraged by the differentiated therapeutic profile of FT516 as an off-the-shelf NK cell therapy administered in the outpatient setting, and its potential to deliver deep and durable responses for patients with advanced B-cell lymphomas, including those that have received prior autologous CAR T-cell therapy," said Wayne Chu, M.D., Senior Vice President of Clinical Development of Fate Therapeutics. "The RMAT designation for the treatment of relapsed / refractory DLBCL reflects the positive clinical data we have observed with FT516 in the dose-escalation stage of our Phase 1 study, and it is an important milestone for the Company that recognizes the unique potential of off-the-shelf, iPSC-derived, NK cell cancer immunotherapy. We look forward to working closely with the FDA to accelerate the development of FT516 in this area of significant unmet medical need with the goal of expanding the reach of transformative cell therapies."

Phase 1 Dose-escalation Efficacy Data

The Phase 1 clinical trial in relapsed / refractory BCL is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single-dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting.

Patients in the dose-escalation stage had received a median of 3.5 prior lines of therapy and a median of three prior lines containing CD20-targeted therapy. As of the data cutoff date of October 18, 2021, four patients in the second dose cohort of 90 million cells per dose, seven patients in the third dose cohort of 300 million cells per dose, and seven patients in the fourth dose cohort of 900 million cells per dose were evaluable for assessment of safety and efficacy (n=18). Of these 18 patients, 10 patients were naïve to treatment with autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy and eight patients were previously treated with autologous CD19-targeted CAR T-cell therapy, including three patients in the fourth dose cohort that were refractory to CAR T-cell therapy (see Table 1).

Table 1. FT516 Phase 1 Dose Cohorts 2, 3 and 4 in Relapsed / Refractory B-cell Lymphoma 1
CAR T Naïve Prior CAR T
Aggressive BCL 2 Indolent BCL 3 Aggressive BCL 4
n 5 5 8
Response 5
Objective Response (%) 4 (80%) 4 (80%) 3 (38%)
Complete Response (%) 2 (40%) 3 (60%) 3 (38%)
Durability of Response 6
Response Rate – 3 Months (%) 4 (80%) 4 (80%) 3 (38%)
Ongoing Responders (%)
Median Follow-up (months) 3 (60%)
8.3 (4.6, 9.9) 3 (60%)
9.9 (3.7, 13.2) 2 (25%)
6.5 (4.6, 8.3)
1 As of data cutoff date of October 18, 2021
2 Includes diffuse large B-cell lymphoma (n=2); high-grade B-cell lymphoma (n=1); transformed indolent lymphoma (n=1); and gray zone lymphoma (n=1)
3 Includes follicular lymphoma (n=3); mantle cell lymphoma (n=1); and marginal zone lymphoma (n=1)
4 Includes diffuse large B-cell lymphoma (n=7) and high-grade B-cell lymphoma (n=1); includes 3 patients refractory to prior CAR T-cell therapy
5 Cycle 2 Day 29 protocol-defined response assessment per Lugano 2014 criteria
6 Measured from initiation of therapy

Of the ten patients naïve to treatment with CAR T-cell therapy, eight patients achieved an objective response (80%), including five patients that achieved a complete response (50%). Three of eight patients previously treated with CAR T-cell therapy achieved an objective response (38%), all of whom achieved a complete response. In each relapsed / refractory BCL disease setting (aggressive BCL naïve to CAR T-cell therapy; indolent BCL naïve to CAR T-cell therapy; aggressive BCL previously treated with CAR T-cell therapy), responses were observed in each of the second, third, and fourth dose cohorts.

All 11 responding patients in the second, third, and fourth dose cohorts continued in ongoing response at three months following initiation of treatment (61%). As of the data cutoff date, eight patients continued in ongoing response (44%) at a median follow-up of 8.3 months:

Three of five patients with aggressive BCL naïve to CAR T-cell therapy continued in ongoing response (60%), with two patients in ongoing response beyond six months (8.3 and 9.9 months) and one patient in ongoing response at 4.6 months;
Three of five patients with indolent BCL naïve to CAR T-cell therapy continued in ongoing response (60%), with two patients in ongoing response beyond six months (9.9 and 13.2 months) and one patient in ongoing response at 3.7 months; and
Two of eight patients with aggressive BCL previously treated with CAR T-cell therapy continued in ongoing response (25%), with responses ongoing at 4.6 and 8.3 months.
The median duration of response in each of the relapsed / refractory BCL disease settings for all responding patients had not been reached.

Phase 1 Dose-escalation Safety Data

No dose-limiting toxicities, and no FT516-related serious adverse events, were observed. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events (TEAEs) of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by investigators (see Table 2). Grade 3 or greater TEAEs related to FT516 were observed in two patients (neutrophil count decreased; and neutropenia and thrombocytopenia). There were no discontinuations due to adverse events. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was observed, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.

Table 2. FT516 Phase 1 TEAEs of Interest in Relapsed / Refractory B-cell Lymphoma
n (%)

DL2 = 90M / dose
(n=4) DL3 = 300M / dose
(n=7) DL4 = 900M / dose
(n=7) Total 1
(n=20)
All Grade Grade 3+ All Grade Grade 3+ All Grade Grade 3+ All Grade Grade 3+
CRS — — — — — — — —
ICANS — — — — — — — —
GvHD — — — — — — — —
Infections 3 (75%) 2 (50%) 2 (29%) 1 (14%) 1 (14%) 1 (14%) 6 (30%) 4 (20%)
CRS = Cytokine Release Syndrome; DL = Dose Level; GvHD = Graft vs. Host Disease; ICANS = Immune Cell-Associated Neurotoxicity Syndrome; M = Million; TEAE = Treatment-Emergent Adverse Event
1 Includes two subjects in the first dose cohort of 30M cells / dose

FT516 RMAT Designation & Dose Expansion

RMAT designation is an FDA program designed to expedite the development and review of regenerative medicine therapies, including cell-based cancer immunotherapies, that have demonstrated the potential to address an unmet medical need based on preliminary clinical evidence. The program allows for early and frequent interactions with the FDA, and enables regulatory authority guidance on efficient drug development, pathways for accelerated approval, and approaches to fulfill post-approval requirements.

The Company has initiated enrollment in the dose-expansion stage of its Phase 1 study of FT516 in combination with rituximab for the treatment of relapsed / refractory BCL at 900 million cells per dose. The Company plans to enroll patients in three disease-specific expansion cohorts using cyclophosphamide and fludarabine as conditioning chemotherapy: patients with relapsed / refractory aggressive lymphomas who have previously been treated with CD19-targeted CAR T-cell therapy; patients with relapsed / refractory aggressive lymphomas who are naïve to treatment with CD19-targeted CAR T-cell therapy; and patients with relapsed / refractory follicular lymphoma. In addition, the Company plans to enroll an expansion cohort without conditioning chemotherapy, combining FT516 with rituximab and bendamustine, a standard-of-care treatment regimen for lymphoma.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of relapsed / refractory acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of relapsed / refractory B-cell lymphoma (NCT04023071).

On December 13, 2021 Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), and Foghorn Therapeutics Inc. (Nasdaq: FHTX), reported a strategic collaboration to create novel oncology medicines by applying Foghorn’s proprietary Gene Traffic Control platform (Press release, Eli Lilly, DEC 13, 2021, View Source [SID1234596918]). The collaboration includes a co-development and co-commercialization agreement for Foghorn’s selective BRM oncology program and an additional undisclosed oncology target. In addition, the collaboration includes three additional discovery programs using Foghorn’s proprietary Gene Traffic Control platform.

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Under the terms of the agreement, Foghorn will receive upfront consideration of $300 million in cash for the collaboration agreement and an equity investment by Lilly of $80 million in Foghorn common shares at a price of $20 per share.

"Oncogenic mutations in BRG1 impact a large population of cancer patients and we believe are best addressed therapeutically with a highly selective BRM inhibitor, though designing such a drug is a difficult chemistry challenge. We’ve been very impressed by the progress the Foghorn team has made against this product profile and are excited to work with this highly talented team," said Jacob Van Naarden, CEO of Loxo Oncology at Lilly and president, Lilly Oncology. "Foghorn has a differentiated platform and we look forward to the prospect of leveraging it to discover multiple new drugs against similarly challenging targets with strong biologic rationale."

"We are excited to be collaborating with the Loxo Oncology at Lilly team to use our platform and utilize Foghorn’s powerful precision biology-first approach to create medicines targeting genetic dependencies within the chromatin regulatory system," said Foghorn CEO Adrian Gottschalk. "This collaboration enables an acceleration and expansion of our pipeline and significantly strengthens our balance sheet as we strive to bring new medicines to patients and their families."

Terms of Collaboration
For the BRM-selective program and the additional undisclosed target program, Foghorn will lead discovery and early research activities, while Lilly will lead development and commercialization activities with participation from Foghorn in operational activities and cost sharing. Foghorn and Lilly will share 50/50 in the U.S. economics, and Foghorn is eligible to receive royalties on ex-U.S. sales starting in the low double-digit range and escalating into the twenties based on revenue levels.

For the additional discovery programs, Foghorn will lead discovery and early research activities. Foghorn may receive up to a total of $1.3 billion in potential development and commercialization milestones. Additionally, Foghorn will have an option to participate in a percentage of the U.S. economics and is eligible to receive tiered royalties from the mid-single digit to low-double digit range on sales outside the U.S. that may be exercised after the successful completion of the dose-finding toxicity studies.

The terms of the transaction have cleared the required waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act).

This transaction will be reflected in Lilly’s reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly’s 2021 non-GAAP earnings per share guidance as a result of this transaction.

About BRM-Selective Program
Data suggest there are over 30 different cancers with brahma-related gene-1 (BRG1) mutations accounting for approximately 5% of all tumors with up to 10% of non-small cell lung cancer tumors, with minimal overlap with other driver mutations. The BRM-selective program is being developed to address BRG1 mutated cancers utilizing two distinct approaches including protein degradation and enzymatic inhibition.

About Foghorn Proprietary Gene Traffic Control Platform
Foghorn’s proprietary Gene Traffic Control platform is a powerful tool for understanding and modulating the chromatin regulatory system. The chromatin regulatory system regulates gene expression by directing the movement of molecules that turn genes on and off. Disease dependencies associated with the chromatin regulatory system are estimated to impact over 2.5 million cancer patients across the U.S., Europe and Japan. This system is further implicated in neurological, autoimmune, and other serious diseases. Foghorn is pursuing multiple treatments for breakdowns in this system and is the only company with the ability to study and target the chromatin regulatory system at scale, in context, and in an integrated way.

On December 13, 2021 CTI BioPharma Corp. (Nasdaq: CTIC) reported that five scientific poster presentations on the pacritinib clinical program at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held as a hybrid (virtual and live) meeting in Atlanta, Georgia, December 11-14, 2021 (Press release, CTI BioPharma, DEC 13, 2021, View Source [SID1234596916]).

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"We are pleased with the growing body of clinical evidence supporting the potential of pacritinib’s unique place in treating cytopenic myelofibrosis, specifically in patients with moderate or severe thrombocytopenia, a notable challenge in light of the significant limitations of approved therapies," said Adam R. Craig, M.D., Ph.D., President and Chief Executive Officer of CTI BioPharma. "Importantly, today we presented data demonstrating that in patients with cytopenic myelofibrosis, full-dose pacritinib yielded higher response rates and a similar safety profile to lower doses of ruxolitinib. Prolonged administration of pacritinib is possible with favorable tolerability in the compassionate use setting, and the use of pacritinib can lead to significant overall and individual symptom relief in patients with both moderate and severe thrombocytopenia."

"As we approach our PDUFA action date of February 28, 2021, we remain focused on bringing forward a new therapeutic option for patients with cytopenic myelofibrosis through our committed collaboration with the FDA."

All presentation materials will be available at ctibiopharma.com.

A Retrospective Head-to-Head Comparison between Pacritinib and Ruxolitinib in Patients with Myelofibrosis and Moderate to Severe Thrombocytopenia (ASH Poster #3639)

Pacritinib, a JAK 2/interleukin-1 receptor–associated kinase 1 (IRAK1) inhibitor that does not inhibit JAK1, is in development for use in patients with myelofibrosis who have thrombocytopenia. Pacritinib was studied in thrombocytopenic patients (platelet count ≤100 x 109/L) in the randomized phase 3 PERSIST-2 trial, which showed pacritinib was superior to best available therapy (BAT), including ruxolitinib, based on spleen volume reduction (SVR) and modified total symptom score (mTSS) response. While many patients in the BAT arm (45%) received ruxolitinib, an analysis of the comparison between pacritinib and ruxolitinib has not been previously performed.

This retrospective head-to-head analysis of pacritinib versus ruxolitinib in "first-line" (ruxolitinib-naïve) patients treated in PERSIST-2 showed that patients with moderate or severe thrombocytopenia were able to maintain full dose intensity with pacritinib. Pacritinib fully dosed at 400 mg/day resulted in numerically higher rates of SVR (28% vs 11%) and mTSS response (37% vs 11%), and a similar safety profile compared with lower doses of ruxolitinib in "first-line" patients with cytopenic myelofibrosis, suggesting that pacritinib may address the unmet medical need of patients with cytopenic myelofibrosis who cannot tolerate full doses of JAK1/2 inhibitors, such as ruxolitinib.

Safety Analysis of Pacritinib in Patients with Myelofibrosis and Severe Thrombocytopenia (ASH Poster #3640)

Pacritinib, a novel JAK2/IRAK1 inhibitor, demonstrated clinically significant activity in spleen volume and symptom reduction in patients with advanced cytopenic myelofibrosis, including those with severe thrombocytopenia (platelet count <50 x 109/L), in phase 2 and 3 clinical trials. Pacritinib, unlike JAK1/2 inhibitors, has demonstrated clinical benefit at the recommended full dose of 200 mg twice daily (BID) in patients with cytopenias in the phase 2 dose–finding PAC203 and phase 3 PERSIST-2 trials.

In this retrospective safety analysis of patients with cytopenic myelofibrosis, including those who had severe thrombocytopenia, the safety profile of pacritinib 200 mg BID was comparable to best available therapy (BAT), which included non-therapeutic options (i.e. supportive care and watch and wait). This analysis suggests that pacritinib 200 mg BID may represent the first fully dosed therapeutic option for patients with cytopenic myelofibrosis, including severe thrombocytopenia.

Long-Term Treatment with Pacritinib on a Compassionate Use Basis in Patients with Advanced Myelofibrosis (ASH Poster #3640)

The efficacy and safety of pacritinib has been evaluated in multiple clinical trials, including two randomized, controlled phase 3 trials (PERSIST-1 and PERSIST-2) and a phase 2 dose-finding trial (PAC203). These trials are unique in the myelofibrosis landscape because they enrolled patients with advanced disease and severe cytopenias. When these trials closed, patients who received pacritinib could apply to continue treatment on a compassionate use basis. This analysis describes pacritinib treatment in this program.

Patients who were treated with pacritinib on PERSIST-1, PERSIST-2, or PAC203 were provided the option to continue receiving pacritinib if they were eligible for the compassionate use program. After receiving pacritinib on an original clinical trial, 75 patients continued to receive pacritinib on a compassionate use basis. Twenty patients were still on pacritinib as of the data cutoff date. Most patients had advanced disease, characterized by cytopenias and circulating blasts.

Median total combined treatment duration (original trial and compassionate use) was 21.1 months (range 0.8 to 80.9 months). Among patients with prior JAK inhibitor exposure, median time from discontinuation from a JAK inhibitor to the last day of known treatment with compassionate use pacritinib was 27.2 months. This duration compares favorably to median survival reported in patients discontinuing ruxolitinib: 14 months overall and about 8 months if the platelet count is <100×109/L.. Prolonged treatment with pacritinib is well-tolerated in patients with advanced myelofibrosis, including those with cytopenias, and reported serious adverse events were consistent with those expected in advanced myelofibrosis patient population and with treatment in a compassionate use setting.

The Impact of Pacritinib on Myelofibrosis Symptoms in Patients with Moderate and Severe Thrombocytopenia: A Retrospective Analysis of Patients in the Persist-2 Trial (ASH Poster #3628)

Pacritinib demonstrated superior spleen volume response versus BAT in patients with myelofibrosis who have moderate or severe thrombocytopenia (platelet count ≤100 x 109/L) in the phase 3 PERSIST-2 trial. Unlike the trials in which JAK1/2 inhibitors were approved, which relied on a modified TSS (mTSS) score that excluded "tiredness," PERSIST-2 included tiredness as part of the TSS.

This retrospective analysis showed that significantly more patients achieved a mTSS response with pooled pacritinib versus BAT (31% vs 14%; P=0.008). More patients achieved a mTSS response with pacritinib 200 mg BID versus BAT (35% vs 14%; P=0.004) and BAT=RUX (35% vs 19%; P=0.110). Patients in the pacritinib 200 mg BID arm experienced greater percent reductions in individual myelofibrosis symptoms between baseline and week 24 compared with BAT, and the severity of physical function symptoms were reduced more with pacritinib 200 mg BID compared with BAT by week 24.

Evidence of NF-ΚB Pathway Activation in Patients with Advanced, High Molecular Risk Myelofibrosis (ASH Poster #3584)

Patients with myelofibrosis who discontinue treatment with ruxolitinib have a poor prognosis that is often associated with advanced phases of disease and severe cytopenias. While these patients are more likely to have high molecular risk (HMR) genomic markers, biological drivers of disease in this advanced population are not well characterized. The interaction between high-risk mutations and cytokine profiles of patients treated in PAC203 were retrospectively analyzed.

In this HMR+ and RAS mutant-enriched cohort of myelofibrosis patients who were intolerant of or resistant to ruxolitinib, a relationship between HMR mutations and an NF-kB directed pro-inflammatory cytokine signature was identified. These results implicate the activation of a distinct biological signaling pathway operative in this molecularly-defined cohort.

About Myelofibrosis and Cytopenias
Myelofibrosis is a bone marrow cancer that results in the formation of fibrous scar tissue and can lead to thrombocytopenia and anemia, weakness, fatigue and an enlarged spleen and liver. Within the U.S. there are approximately 21,000 patients with myelofibrosis, 7,000 of which have severe thrombocytopenia (defined as blood platelet counts of less than 50 x109/L). Severe thrombocytopenia is associated with poor survival and high symptom burden and can occur as a result of disease progression or from drug toxicity with other JAK2 inhibitors such as JAKAFI and INREBIC.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R, but not JAK1. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and chronic lymphocytic leukemia (CLL), due to its inhibition of c-fms, IRAK1, JAK2 and FLT.

On December 13, 2021 Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS), reported positive results of an interim analysis of overall survival from the pivotal study "CHOICE-01" (NCT03856411), a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab plus standard-of-care chemotherapy as the first-line treatment of advanced squamous or non-squamous non-small cell lung cancer ("NSCLC") (Press release, Coherus Biosciences, DEC 13, 2021, View Source [SID1234596915]). This interim analysis demonstrated a statistically significant improvement in overall survival, crossing the prespecified efficacy boundary, in patients treated with toripalimab plus chemotherapy. This treatment effect was observed notwithstanding the effects of active crossover to toripalimab at disease progression for patients in the control (placebo plus chemotherapy) arm. As previously reported at the 2021 World Conference on Lung Cancer (WCLC), the study also met the primary endpoint of progression free survival (PFS) per RECIST v1.1 for the toripalimab arm as compared to chemotherapy alone.

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Junshi Biosciences and Coherus plan to submit the CHOICE-01 results for publication and request a meeting with the United States Food and Drug Administration ("FDA") to discuss the submission of a Biologics License Application ("BLA") supplement for toripalimab in combination with chemotherapy for the first-line treatment of advanced NSCLC. The BLA for toripalimab in combination with gemcitabine and cisplatin for the first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma ("NPC") and toripalimab monotherapy for the second-line or above treatment of recurrent or metastatic NPC after platinum-containing chemotherapy is currently under priority review by the FDA.

"The achievement of an overall survival benefit in non-small cell lung cancer patients by toripalimab is a watershed event in the strategic transformation of Coherus and validates the role of toripalimab as the foundation of our immuno-oncology pipeline," said Denny Lanfear, CEO of Coherus. "Toripalimab has once again delivered positive progression free survival and overall survival clinical data in a first-line setting. We will now work closely with our partners at Junshi Biosciences to engage the FDA on BLA supplement filing strategies for first-line treatment of non-small cell lung cancer. We also look forward to initiating future studies combining toripalimab with a series of complementary immuno-oncology agents to advance patient care and outcomes in oncology."

"The results of CHOICE-01, demonstrating improvements in overall survival, confirm that toripalimab can deliver significant benefits to patients receiving first-line treatment for non-small cell lung cancer," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "With a consistently strong record of positive efficacy and safety accumulating as data read out from studies across multiple tumor types, we are working to register toripalimab for a broad array of indications in China and the United States. In 2022, we look forward to clinical data from additional Phase 3 studies in NSCLC, small cell lung cancer, triple negative breast cancer, and hepatocellular cancer."

About CHOICE-01
A total of 465 treatment-naive advanced NSCLC patients (220 squamous and 245 non-squamous) were randomized (2:1): 309 patients to the toripalimab plus chemotherapy arm and 156 to the placebo plus chemotherapy arm. The primary endpoint was PFS assessed by the investigator. Secondary endpoints included PFS assessed by a blinded independent review committee (BIRC), overall survival (OS), objective response rate (ORR) and duration of response (DoR). Patients in the placebo plus chemotherapy arm were actively crossed-over to toripalimab treatment at disease progression. The addition of toripalimab to standard first-line chemotherapy in patients with advanced NSCLC showed a manageable safety profile with no new safety signals observed.

About toripalimab

Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 is thought to recharge the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are 4 approved indications for toripalimab in China:

second-line treatment of unresectable or metastatic melanoma;
recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy;
locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC.
The first three indications have been included in the National Reimbursement Drug List (NRDL) (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the first and second indications (melanoma and NPC).

In addition, two supplemental New Drug Applications (NDAs) for toripalimab were accepted by the National Medical Products Administration (NMPA) for review in China:

first-line treatment of patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC).
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) with no EGFR or ALK tumor aberrations.
In the United States, the FDA has granted priority review for the toripalimab BLA for the treatment of recurrent or metastatic NPC, an aggressive head and neck tumor which has no FDA-approved immuno-oncology treatment options. Earlier, the FDA granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designation for the treatment of esophageal cancer, NPC, mucosal melanoma and soft tissue sarcoma. Earlier in 2021, Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple other cancer types.

On December 13, 2021 Celularity Inc. (Nasdaq: CELU) ("Celularity") reported that preclinical data on the development of its placental-derived allogeneic genetically modified NK cell therapy program (CYNK-101) and its placenta-derived allogeneic CAR-NK cell therapy program (CAR19-CYNK), respectively (Press release, Celularity, DEC 13, 2021, View Source [SID1234596914]). The Company reported its findings in two poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition (ASH) (Free ASH Whitepaper) taking place in Atlanta and virtually December 11-14, 2021 .

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Poster no. 2773: "Human Placental CD34+-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) in Combination with Daratumumab for Immunotherapy Against CD38 Expressing Hematological Malignancies"

Session name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation date/time: Sunday, 12 December 2021; 6:00 pm
Room: Georgia World Congress Center, Hall B5
Highlights: CYNK-101 is a cryopreserved, off the shelf, allogeneic NK cell product candidate, overexpressing a high IgG binding affinity, proteinase cleavage resistant, CD16 variant. The results show the synergistic effect of combining CYNK-101 with daratumumab to drive antibody dependent cellular cytotoxicity activity against CD38+ hematological malignancies in vitro and in vivo. In these studies, CYNK-101 was not susceptible to daratumumab-directed fratricide and did not display on-target, off-tumor cytotoxicity, suggesting CYNK-101 may be a unique NK cell platform that preserves innate immune function in the presence of daratumumab.

Poster no. 2779: "Development of CD19 CAR Engineered Human Placental CD34+-Derived Natural Killer Cells (CAR19-CYNK) As an Allogeneic Cancer Immunotherapy"

Session name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation date/time: Sunday, 12 December 2021; 6:00pm
Room: Georgia World Congress Center, Hall B5
Highlights: The results demonstrate the feasibility and functionality of expressing a Chimeric Antigen Receptor (CAR) directed to CD19 on placental CD34+ derived, cryopreserved, off-the-shelf, allogeneic CYNK cells. The introduction of CAR in the product candidate CAR19-CYNK did not impact performance of CYNK cell manufacture and endowed additional tumor cell killing against resistant lymphoma cell lines in a CD19-dependent manner, when tested both in vitro and in vivo.