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.

On December 13, 2021 Bristol Myers Squibb (NYSE: BMY) reported that on December 10, 2021, its Board of Directors approved an increase in the quarterly dividend and authorized an additional multi-year share repurchase program (Press release, Bristol-Myers Squibb, DEC 13, 2021, View Source [SID1234596913]).

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"The company’s financial position is strong, and we remain committed to a consistent, balanced capital allocation strategy," said Giovanni Caforio, board chair and chief executive officer, Bristol Myers Squibb. "With significant free cash flow of $45 billion to $50 billion expected between 2021 and 2023, investment in business development continues to be a key priority for the company in driving innovation and sustained growth as we return capital to shareholders through the dividend increase and expanded share repurchase authorization. We remain committed to maintaining a strong investment grade credit rating and reducing our debt."

Increase in 2022 Dividend

The Board of Directors has declared a quarterly dividend of fifty-four cents ($0.54) per share on the $.10 par value common stock of the company. The dividend is payable on February 1, 2022 to stockholders of record at the close of business on January 7, 2022.

This amount represents a 10.2% increase in the quarterly dividend over last year’s quarterly rate of forty-nine cents ($0.49) per share. At this quarterly dividend rate, subject to the normal quarterly review by the Board of Directors, the annual dividend rate for the fiscal year 2022 is $2.16 per share. This marks the thirteenth consecutive fiscal year that Bristol Myers Squibb increased its dividend payouts.

In addition, the Board of Directors has declared a quarterly dividend of fifty cents ($0.50) per share on the company’s $2.00 convertible preferred stock, payable March 1, 2022 to stockholders of record at the close of business on February 1, 2022.

Multi-Year Share Repurchase Authorization

The Board of Directors also authorized the repurchase of an additional $15 billion of the company’s common stock. With this increase, the company’s total outstanding share repurchase authorization is approximately $15.2 billion. This multi-year authorization enables management to execute repurchases at its discretion.

The timing and amount of any share repurchases under the authorization will be determined by management at its discretion and based on market conditions and other considerations. Share repurchases under the authorizations may be made through a variety of methods, which may include open market purchases, pursuant to pre-set trading plans meeting the requirements of Rule 10b-1 under the Securities Exchange Act of 1934, in privately negotiated transactions, block trades, accelerated share repurchase transactions, or any combination of such methods. The program does not obligate Bristol Myers Squibb to acquire any particular amount of its common stock, and the repurchase program may be suspended or discontinued at any time at the company’s discretion.

On December 13, 2021 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported a poster highlighting the safety and preliminary efficacy data of its Phase 2 study of prexigebersen (BP1001) was presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place from December 11-14, 2021 (Press release, Bio-Path Holdings, DEC 13, 2021, View Source [SID1234596912]).

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The poster, titled, "Safety and Efficacy of Lower Intensity Induction Therapy with Intravenous Prexigebersen (BP1001) in Patients with High-Risk and Relapsed/Refractory Acute Myeloid Leukemia (AML)," was presented by Maro Ohanian, D.O., Department of Leukemia, University of Texas MD Anderson Cancer Center. The poster described the safety and preliminary efficacy of Bio-Path’s lead drug candidate, prexigebersen (liposomal Grb2 antisense), from a Phase 2 study in combination with decitabine or decitabine plus venetoclax as a potential treatment for patients diagnosed with AML.

"Our study’s novel clinical trial protocol was designed to adjust for the inclusion of newly approved therapies that we believed would be enhanced from combination with our DNAbilize technology," said Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "This robust design provided for early evaluation of various combinations of prexigebersen to optimize the best potential outcomes for patients and allows for the most expeditious pathway to market. We are delighted to have these safety and preliminary efficacy data presented among an audience dedicated to bringing new cancer treatments to patients."

The Phase 2 clinical trial is a multi-center, open label study with three patient cohorts:

•Untreated AML patients treated with prexigebersen in combination with decitabine plus venetoclax;
•Refractory/relapsed AML patients treated with prexigebersen in combination with decitabine plus venetoclax; and
•Refractory/relapsed AML patients, resistant or intolerant to venetoclax, treated with prexigebersen in combination with decitabine.

The primary objective of the study is to assess whether prexigebersen in combination with decitabine plus venetoclax provides higher response rates than decitabine plus venetoclax in AML patients and whether prexigebersen in combination with decitabine provides higher response rates than decitabine alone in AML patients. The study was amended to obtain safety run-in data for patients treated with prexigebersen + decitabine first before proceeding to safety run-in for patients treated with prexigebersen + decitabine + venetoclax. In the Poster we report the safety run-in and efficacy data of AML patients treated with prexigebersen + decitabine or prexigebersen + decitabine + venetoclax.

Data Highlights

Six patients, including four patients (67%) with de novo AML and two secondary AML patients (33%), were treated with at least one cycle of prexigebersen + decitabine combination therapy. All patients in this cohort (median age 72 years) were considered high risk due to having either adverse risk status by ELN (n=5) or treated secondary AML (n=1). Data showed that adverse events (AEs) were generally consistent with those expected with decitabine and/or AML. Three of the six patients (50%) had a response, including two de novo patients (33%) who achieved a CRi (complete remission with incomplete blood count recovery) and one secondary AML patient (17%) who achieved a partial remission (PR). Patients with these conditions generally have a less than 20% CR/CRi response rate.

Six patients were treated with at least one cycle of prexigebersen + decitabine + venetoclax combination therapy. Of the six patients, two (33%) had de novo AML and four (67%) were relapsed/refractory. All patients in this cohort were adverse-risk by ELN (n=2) or relapsed/refractory (n=4). AEs were generally consistent with decitabine and venetoclax treatment and/or for AML. Four patients (67%) achieved a complete remission (CR)/CRi/morphological leukemia free state (MLFS) (n=1/2/1) and one (17%) achieved a PR. Of these five patients, three were relapsed/refractory (75% of relapsed/refractory patients) (1 CR/1 CRi/1 MLFS) and two were de novo (1 CRi/1 PR) (100% of the de novo patients). CR rates to combination treatment with decitabine and venetoclax for relapsed/refractory AML patients are 42-52%1,2 and 0-39%1,2 for relapsed/refractory secondary AML patients.

The preliminary efficacy data are compelling and show that prexigebersen -based combination therapy was not only safely administered to high-risk and relapsed/refractory AML patients considered unsuitable for standard chemotherapy, but also

demonstrated encouraging efficacy signals. This is particularly encouraging as relapsed/refractory patients are a challenging population in which current treatment options are suboptimal.

About Prexigebersen (BP1001)

Prexigebersen is a neutral liposome incorporated with nuclease-resistant, hydrophobic P-ethoxy antisense oligodeoxynucleotides targeted to Grb2 mRNA. Grb2 is an adaptor protein that links oncogenic tyrosine kinases with downstream kinases, such as ERK and AKT, which are critical to cell proliferation and survival.