Stockwinners Market Radar for December 11, 2022 - Earnings, Upgrades downgrades, option trades, Best Stock Advisory Service

20:14 EST Fly Intel: Top five weekend stock stories - Catch up on the weekend's top five stories with this list compiled by The Fly: 1. Amgen (AMGN) is in advanced talks to buy drug company Horizon Therapeutics (HZNP) in a takeover likely to be valued at well over $20 billion and mark the largest healthcare merger of the year, The Wall Street Journal's Ben Dummett, Dana Cimilluca, and Laura Cooper report, citing people familiar with the matter. A deal could be finalized by Monday assuming the talks with Amgen don't fall apart, the people said. 2. Boston Scientific (BSX) and Acotec Scientific announced that Boston Scientific will make a partial offer to acquire a majority stake, up to a maximum of 65%, of shares of Acotec, a Chinese medical technology company that offers solutions designed for a variety of interventional procedures. The proposed price is HK$20 per share, which represents a total upfront cash payment consideration of approximately $523 million for the 65% stake at current exchange rates. 3. Almost every tech stock is cheaper than a year ago, and there is temptation to bottom-fish, but there's a big difference between cheap and cheaper, though, Eric J. Savitz writes in this week's edition of Barron's. There are bargains to be had if investors look hard enough and have a little patience, with IAC (IAC) looking like a textbook case of an undervalued stock that deserves more attention, the author contends. 4. Marvel and Disney's (DIS) "Black Panther: Wakanda Forever" easily won this weekend's domestic box office with an estimated $11.1M in its fifth outing for a total of $409.8M. The movie has earned $767.8M worldwide. The weekend was uneventful otherwise, with overall ticket sales coming in at $37M, the second-worst of the year after the weekend of January 28-30, according to CinemaScore. 5. Regal Rexnord (RRX), Moody's (MCO), Philip Morris (PM), Zoetis (ZTS), Mastercard (MA), BlackRock (BLK), Lam Research (LRCX), Visa (V), Texas Instruments (TXN), Old Dominion (ODFL), Paychex (PAYX), Microsoft (MSFT), MarketAxess (MKTX), Copart (CPRT), Monolithic Power Systems (MPWR), Arista Networks (ANET), and Charles Schwab (SCHW) saw a positive mention in this week's edition of Barron's.

18:45 EST CTI BioPharma presents new anemia benefit data from pacritinib program - CTI BioPharma announced an oral presentation and two poster presentations from the company's pacritinib program at the 64th American Society of Hematology Annual Meeting and Exposition, taking place in New Orleans, Louisiana and virtually December 10-13, 2022. A new post-hoc data analysis from the Phase 3 PERSIST-2 trial of pacritinib, a novel JAK2/IRAK1 inhibitor approved by the U.S. Food and Drug Administration for patients with myelofibrosis and severe thrombocytopenia, highlights pacritinib's potential anemia benefit in patients with myelofibrosis through its inhibition of Activin A receptor type 1. Pacritinib demonstrated hemoglobin improvement in the randomized Phase 3 PERSIST-2 study, though the mechanism behind and the extent of pacritinib's anemia benefit has not been fully described. A retrospective analysis of the Phase 3 PERSIST-2 study was performed to assess pacritinib's in vitro potency against ACVR1 and its ability to reduce hepcidin and to describe the impact of pacritinib 200 mg BID on RBC transfusion independence. Results from in vitro testing suggest pacritinib is a potent ACVR1 inhibitor that reduces hepcidin expression. Analysis of the clinical data shows that pacritinib therapy results in transfusion independence in patients with myelofibrosis who require RBC transfusions. Given this unique mechanism of action, pacritinib may provide a therapeutic option that provides spleen, symptom and anemia benefits to patients with myelofibrosis. A retrospective analysis of baseline data from the Phase 3 PERSIST-1 and Phase 2 PAC203 trials was performed to describe the differential impact of thrombocytopenia and anemia on symptom burden by analyzing symptom data from patients with myelofibrosis who have isolated thrombocytopenia versus isolated anemia. Results showed that patients with isolated thrombocytopenia had more severe symptom burden than those with isolated anemia, particularly with physical function- and spleen-related symptoms. While amelioration of anemia is an important therapeutic goal for patients with cytopenic myelofibrosis, these data suggest that additional efforts aimed at the control of platelet count and underlying disease should be implemented to achieve optimal symptom control. Pacritinib is a novel JAK2/IRAK1/ACVR1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and severe thrombocytopenia. So far, treatment options for patients with myelofibrosis and severe thrombocytopenia are limited due to the high incidence of treatment-related thrombocytopenia when other JAK inhibitors are used. Previously, pacritinib demonstrated clinical activity in myelofibrosis in two Phase 3 studies -- PERSIST-1 and PERSIST-2 -- and a Phase 2 dose-finding study, all of which included patients with severe thrombocytopenia. PACIFICA is a multinational, multicenter, 2:1 randomized, controlled Phase 3 trial designed to confirm the efficacy and safety of pacritinib 200 mg twice daily vs physician's choice therapy in patients with myelofibrosis and severe thrombocytopenia.

18:05 EST Blueprint announces AYVAKIT data showing durable response rates, prolonged OS - Blueprint Medicines announced AYVAKIT data showing high, durable response rates and prolonged overall survival in patients with advanced systemic mastocytosis, including SM with an associated hematological neoplasm. Long-term follow-up of 38 treatment-naive patients from the PATHFINDER trial and 69 patients from the EXPLORER trial - regardless of line of therapy - further validate the clinical efficacy and safety profile of AYVAKIT in advanced SM. Based on modified IWG-MRT-ECNM criteria, the overall response rate was defined as complete remission with full or partial recovery of peripheral blood counts, partial remission or clinical improvement. All responses were confirmed. In the PATHFINDER trial, AYVAKIT showed broad clinical activity in treatment-naive patients evaluable for response, including those with SM-AHN, as of a data cutoff date of April 20, 2021. For treatment-naive patients across advanced SM subtypes: ORR was 84 percent and CR/CRh rate was 32 percent. Median time to response was two months and median time to CR/CRh was six months. Median duration of response has not been reached. Estimated 24-month OS rate was 88 percent. For treatment-naive patients with SM-AHN: ORR was 95 percent and CR/CRh rate was 37 percent. Estimated 24-month OS rate was 86 percent. In addition, improvements were observed across hematologic parameters, such as monocytes and eosinophils in the peripheral blood, suggesting multi-lineage involvement of the KIT D816V mutation. In the EXPLORER trial, 57 patients across lines of therapy were evaluable for response as of a data cutoff date of April 5, 2022. The ORR was 77 percent, with median DOR and OS not reached in patients followed for up for six years. Safety data from the PATHFINDER and EXPLORER trials were consistent with previously reported results and the FDA approved labeling for AYVAKIT, and reinforce the favorable benefit-risk profile of AYVAKIT at the 200 mg once-daily recommended dose. The most common treatment-related adverse events included periorbital edema, thrombocytopenia, peripheral edema, anemia and nausea. Discontinuations due to treatment-related AEs occurred in four treatment-naive patients since the initiation of the PATHFINDER trial in 2018, and seven patients across lines of therapy since the initiation of the EXPLORER trial in 2016. In addition, Blueprint Medicines announced top-line, 12-week results from the dose-finding Part 1 of the HARBOR trial of elenestinib, a next-generation KIT D816V inhibitor, reflecting the company's long-term commitment to SM. HARBOR Part 1 was designed to assess concurrent dose cohorts of elenestinib plus best available therapy versus placebo plus best available therapy in patients with indolent SM. The trial included 29 patients in the elenestinib group, and 10 patients in the placebo group. Elenestinib showed evidence of clinical activity and safety consistent with its preclinical profile and a completed Phase 1 healthy volunteer trial. Elenestinib treatment led to rapid improvements in objective measures of mast cell burden, including serum tryptase and KIT D816V allele fraction, and total symptom score as measured by the Indolent SM Symptom Assessment Form. At 12 weeks, elenestinib demonstrated similar reductions in TSS across dose cohorts. In addition, consistent with previously reported data from the PIONEER trial of AYVAKIT in indolent SM, change in serum tryptase was not correlated with change in TSS. Safety results show that elenestinib was generally well-tolerated, and there were no discontinuations due to AEs. Blueprint Medicines plans to present data from Part 1 of the HARBOR trial at a medical congress in 2023.

17:57 EST Kite announces findings from two new analyses of ZUMA-7 trial of Yescarta - Kite, a Gilead company, announced findings from two new analyses of the landmark ZUMA-7 trial of Yescarta, the largest and longest follow-up of a CAR T-cell therapy versus standard of care in patients with relapsed or refractory large B-cell lymphoma. These results include an analysis of outcomes for patients who received subsequent treatment for their lymphoma following second-line Yescarta therapy or SOC therapy, as well as an exploratory analysis of the association between metabolic tumor volume and clinical outcomes. Data from the pivotal ZUMA-7 trial supported the U.S. Food and Drug Administration's expanded approval of Yescarta in April 2022 as initial treatment in adults with r/r LBCL that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy, and led to a similar approval by the European Medicines Agency in October 2022. In an analysis of patients from the ZUMA-7 trial who required subsequent therapy following second-line treatment, 47% of patients randomized to receive Yescarta in the second-line required subsequent therapy compared to 71% patients randomized to 2L standard of care. For patients who received third-line chemotherapy following treatment with Yescarta, overall median progression-free survival was 1.7 months and median overall survival was 8.1 months since 3L treatment initiation, with an objective response rate of 25%. Among Yescarta patients who received 3L cellular immunotherapy, median PFS was 3.5 months, and six patients went on to receive subsequent stem cell transplant, with all six alive at data cutoff. Of the patients who received retreatment with CAR T-cell therapy in 3L, but did not progress on to stem cell transplant, one had fatal disease progression at 8.7 months following retreatment, and one had a complete response and was alive at data cutoff (8.4 months following retreatment). Thirty-four of these patients received 3L chemotherapy following initial response to 2L Yescarta. Among those patients, overall median PFS was 1.7 months and median OS was 8.1 months, with an ORR of 32%. Among patients randomized to SOC who received 3L cellular immunotherapy, median PFS was 6.3 months and median OS was 16.3 months. In an analysis from ZUMA-7 of the association of metabolic tumor volume and clinical outcomes, event-free survival was superior for Yescarta compared to SOC for patients with high and low MTV. EFS trended shorter in Yescarta patients with high MTV and EFS was shorter in SOC patients with high MTV. Similarly, PFS with Yescarta was superior to SOC for both low and high MTV. In the Yescarta arm, median MTV was higher in patients who experienced Grade greater than or equal to3 neurologic events or Grade greater than or equal to3 cytokine release syndrome compared with patients who experienced Grade 1-2 or no neurologic events or Grade 1-2 or no CRS, respectively.

17:49 EST Cogent Biosciences announces updated data from ongoing Phase 2 APEX trial - Cogent Biosciences announced updated clinical data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis. APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. As of the data cutoff date of October 26, 2022, 16 patients had been treated in Part 1 at one of four dose levels. The median age of patients at study entry was 69 years. Patients were enrolled with the following sub-types: three patients with aggressive systemic mastocytosis, 12 patients with systemic mastocytosis with associated hematologic neo-plasm, and one patient with mast cell leukemia. Three patients had received prior avapritinib and midostaurin treatment. As of the cutoff date October 26, 2022, bezuclastinib was generally well-tolerated at all doses. The majority of adverse events were Grade 1/2 and occurred in no more than one patient. Importantly, there were no related cases of cognitive impairment and no reported intracranial bleeding events, which have been associated with other KIT inhibitors. Limited low-grade edema was observed, and analysis of platelet counts in bezuclastinib-treated patients showed no trend in platelet reduction at any dose. As of the cutoff date of October 26, 2022, 11 patients were evaluable for response per the modified IWG-MRT-ECNM criteria, and 12 patients were evaluable for response using pure pathological response criteria. Reported ORR per mIWG-MRT-ECNM criteria includes centrally adjudicated confirmed and unconfirmed CR, CRh, PR, and CI.

16:48 EST Incyte's novel mutant CALR antibody unveiled at ASH 2022 - Incyte announced new research detailing the development and mechanism of action of INCA033989, an Incyte-discovered, investigational novel anti-mutant calreticulin-targeted monoclonal antibody. Pre-clinical data indicate that INCA033989 can alter disease course by reducing mutant CALR allele burden and thus may be an efficacious and safe treatment in patients with myelofibrosis and essential thrombocythemia. INCA033989 binds with high affinity to mutant CALR and inhibits oncogenesis, the process of cells becoming cancerous, in cells expressing this oncoprotein. INCA033989 potently antagonizes CALR oncogenic function, resulting in selective inhibition of JAK/STAT signaling only in CALR-mutated cells with no effect on normal, non-oncogenic cells. This selectivity of action with INCA033989 results in the specific killing of tumor cells harboring the mutation and is suggestive of the potential to alter the course of disease in patients with CALR-mutant MF and ET.

16:42 EST Regeneron announces data from trials evaluating investigational odronextamab - Regeneron Pharmaceuticals announced positive new and updated data from a Phase 1 and pivotal Phase 2 trial -- ELM-1 and ELM-2 -- evaluating investigational odronextamab in patients with relapsed/refractory diffuse large B-cell lymphoma. These included first data from a Phase 2 cohort of patients naive to prior CAR-T therapy, as well as updated data from a dose expansion cohort of a Phase 1 trial in patients who had progressed on CAR-T therapy. The results were presented in an oral session at the 64th American Society of Hematology Annual Meeting and Exposition in New Orleans, LA, and will form the basis of planned submissions to regulatory authorities in 2023, including to the U.S. Food and Drug Administration. Odronextamab is an investigational bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing. At ASH, efficacy in R/R DLBCL was presented from 130 CAR-T naive patients in a Phase 2 cohort and 31 CAR-T experienced patients in a dose expansion cohort of a Phase 1 trial. All patients had received at least two prior therapies, including a CD20 antibody and alkylating agent. Patients were treated with a step-up regimen of odronextamab in the first cycle to help mitigate the risk of cytokine release syndrome before receiving the full dose of 160 mg. The step-up regimen was modified part way through the trial to further mitigate CRS. Among CAR-T naive patients, a 49% objective response rate, with 31% achieving a complete response. The median duration of complete response was 18 months. Among post-CAR-T patients, a 48% ORR, with 32% achieving a CR. The mDOCR was not reached. Among 140 patients in the Phase 2 cohort assessed for safety, adverse events occurred in 99% of patients, with 79% being greater than or equal to Grade 3. Discontinuations due to an AE occurred in 10% of patients, and there were 5 deaths due to pneumonia, COVID-19 and pseudomonal sepsis where the relationship to odronextamab treatment could not be excluded. CRS was the most common AE, of which 64% of cases were mild and all resolved within a median time of 2 days. There were no Grade 4 or 5 CRS cases, and the incidence of Grade 2 or higher cases was reduced with the modified step-up regimen when compared to the original. Based on these data, the OLYMPIA Phase 3 development program investigating odronextamab in earlier stages of the disease is in the process of being initiated. In the U.S., odronextamab has been granted Fast Track Designation for DLBCL by the FDA. In the European Union, Orphan Drug Designation was granted for DLBCL by the European Medicines Agency. Odronextamab is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.

16:21 EST Vincerx Pharma presents preclinical data on VIP943 in AML models - Vincerx Pharma announced a poster presentation of preclinical data of Vincerx's proprietary payload and linker technology and VIP943, the Company's internalizing ADC targeting CD123, at the 64th American Society of Hematology Annual Meeting 2022. VIP943 is a novel ADC, which binds to the IL3-receptor alpha chain. VIP943 combines the unique payload class of kinesin spindle protein inhibitors with a proprietary legumain-cleavable linker. Vincerx's CellTrapper modification of the KSPi prevents diffusion out of the cell, allowing intracellular accumulation. The nonpermeability of the payload prevents off-target toxicities, leading to favorable efficacy and safety profiles. Bone marrow samples derived from patients with AML were used to evaluate VIP943 monotherapy at different concentrations in a depletion and a proliferation assay. Combination treatment of VIP943 and venetoclax was evaluated. All patient samples were analyzed by flow cytometry and were positive for CD123 cell surface expression. In the depletion assay, only the samples which showed spontaneous proliferation were sensitive to VIP943 treatment in accordance with the mode of action of the KSPi payload. In a patient-derived AML xenograft model, the triple combination of VIP943 with venetoclax and azacitidine increased the number of complete responses and the overall survival compared with venetoclax and azacitidine. VIP943 did not induce cytokine release in a human cytokine release assay when compared with positive controls. One dose of VIP943 in an immunophenotyping study in NHP resulted in a reversible reduction in CD123+ basophils. In a NHP safety study, a newly generated ADC using a gemtuzumab biosimilar as the targeting antibody conjugated to our effector chemistry comprised of a proprietary linker and payload and VIP943 were directly compared with Mylotarg. CD33+/CD123+ basophils showed an expected decrease across treatments; however, the VIP943 and Gem-KSPi ADC groups demonstrated a full recovery over the observation period, whereas Mylotarg showed an increased severity. Over time, a significant deleterious effect was seen with a single dose of Mylotarg on platelets, WBC count, reticulocytes, hemoglobin, hematocrit and lymphocytes. In contrast, a single dose of Gem-KSPi ADC and VIP943 showed no effects on hematology parameters other than the aforementioned transient reduction of CD123+ basophils. Evaluation of serum chemistry showed increases in liver function enzymes, bilirubin and urea nitrogen in the Mylotarg group. The female monkey treated with Mylotarg died before the end of the observation period and the male monkey had to be euthanized. All monkeys from the Gem-KSPi ADC and VIP943 groups were healthy and returned to the colony with no remarkable changes in serum chemistry. Overall, these results demonstrate the substantial advancement in ADC technology with the development of VIP943. Further IND-enabling studies are ongoing, and the company expects to file an IND in mid-2023.

16:14 EST Innate Pharma presents data from ongoing Phase 2 TELLOMAK trial - Innate Pharma presented data from a preliminary analysis of the TELLOMAK Phase 2 trial demonstrating clinical activity and a favorable safety profile for lacutamab, a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, in patients with advanced Sezary syndrome, a form of T cell lymphoma. The data were presented during the 2022 ASH Annual Meeting, in New Orleans. At the time of data cut off, the Intention To Treat population included 37 post mogamulizumab patients with advanced, highly refractory Sezary syndrome, and 35 patients were Evaluable for Efficacy. The patient population was heavily pre-treated with a median of 6 prior lines of therapy. The median follow-up was 10.9 months. In the ITT population, the global objective response rate was 21.6%. ORR in the blood was 37.8%, with 21.6% achieving complete response. ORR in the skin was 35.1%. In the EES population, global objective response rate was 22.9%. ORR in the blood was 40.0% and ORR in the skin was 37.1%. Within the subgroup of patients that achieved a global response, median duration of global response was 10.8 months with median time to global response of 4 months; median time to blood response was 1.0 month and median time to skin response was 2.8 months. In line with previous observations, lacutamab demonstrated a favorable safety profile for patients with advanced Sezary syndrome in the TELLOMAK Phase 2 preliminary analysis. Grade greater than or equal to 3 Treatment-related Treatment-Emergent Adverse events were observed in 6/37 patients.

16:08 EST Adicet Bio reports data from ongoing ADI-001 Phase 1 trial - Adicet Bio announced safety and efficacy data from the company's ongoing Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell NHL. The company believes these data continue to support the potential of Adicet's investigational gamma delta CAR T cell therapy to provide significant benefit both in terms of anti-tumor activity and safety. Based on the study findings as of a December 5, 2022 data-cut date, Adicet plans to transition ADI-001 into a potentially pivotal program in the second quarter of 2023. Of the 16 evaluable patients, three received ADI-001 at dose level 1, three received ADI-001 at DL2, three received ADI-001 at DL3, one received two infusions of ADI-001 at DL3, and six received ADI-001 at DL4. On an exploratory basis, primarily to understand safety and pharmacokinetics of a second ADI-001 dose, the first and second patient in DL3 while testing negative for minimal residual disease and in CR, received a second DL3 dose, three and two months after the first infusion, respectively. Patients were heavily pretreated with a median number of prior therapies of four and had a poor prognostic outlook based on their median International Prognostic Index score. ADI-001 treatment demonstrated a 75% ORR and 69% CR rate in the study across all dose levels. In five LBCL patients that previously relapsed after prior autologous anti-CD19 CAR T therapy, treatment with ADI-001 demonstrated 100% ORR and CR rate. These patients included a triple-hit high-grade B-cell lymphoma patient, three diffuse large B-cell lymphoma patients, and a double-hit high-grade B-cell lymphoma patient. ADI-001 resulted in CR in patients who previously showed a partial response to autologous CAR T. An 86% CR rate was observed in LBCL patients across DL3 and above. 75% CR rate in LBCL across all dose levels. Both DL2 and DL3 demonstrated a six-month CR rate of 33%; Patient follow up continues in DL4 to assess six-month durability. Circulating ADI-001 cells were visible through day 28 in peripheral blood at DL4. ADI-001 was generally well-tolerated in the study to date. There were no occurrences of dose-limiting toxicities, graft vs host disease, or Grade 3 or higher Cytokine Release Syndrome or immune effector cell-associated neurotoxicity syndrome reported. Enrollment in the Phase 1 clinical study of ADI-001 is currently ongoing to provide additional durability data and further support the recommended Phase 2 dose.

15:57 EST Fate presents interim data from dose-escalation stage of Phase 1 study of FT819 - Fate Therapeutics presented interim clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT819 for patients with relapsed / refractory B-cell lymphoma at the 64th American Society of Hematology Annual Meeting and Exposition. The landmark trial is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master induced pluripotent stem cell line, a renewable cell source that enables mass production of engineered T-cell therapies with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 incorporates several first-of-kind features including the integration of a novel CD19-targeted 1XX chimeric antigen receptor construct into the T-cell receptor alpha constant locus, which is intended to promote uniform CAR expression, enhance T-cell potency, and prevent graft-versus-host disease. The multi-center Phase 1 clinical trial of FT819 is designed to assess its safety and clinical activity in adult patients with r/r BCL and to determine the recommended Phase 2 dose and schedule. As of the September 8, 2022 data cutoff date, 10 patients with aggressive large B-cell lymphoma have been treated with FT819, including 8 patients in Regimen A with a single dose of FT819 and 2 patients in Regimen B with three fractionated doses of FT819 on Days 1, 3, and 5. Patients received standard conditioning chemotherapy consisting of cyclophosphamide at 500 mg/m2 and fludarabine at 30 mg/m2 for 3 days prior to the initiation of each regimen. Patients were heavily pre-treated having received a median of 4 prior lines of therapy, including 7 of 10 patients having previously received autologous CD19-targeted CAR T-cell therapy. As of the September 8, 2022 data cutoff date, an additional 5 patients with r/r BCL have been treated with FT819. One patient with Grade 3a follicular lymphoma treated in Regimen A with a single dose of FT819 at 180 million cells achieved a complete response at Day 30. Four patients with Richter's Transformation did not respond to therapy at Day 30. No dose-limiting toxicities, and no Grade 3 or greater FT819-related adverse events or serious AEs, were observed. Of the 15 patients treated in Regimens A and B, three patients experienced Grade 2 cytokine release syndrome characterized by fever, hypotension, and hypoxia, which events resolved with single-dose tocilizumab and supportive care. No treatment-emergent AEs of any grade of immune effector cell-associated neurotoxicity syndrome or graft-versus-host disease were reported by investigators. The FT819 treatment regimen was well tolerated. Grade 3 or greater TEAEs not related to FT819 primarily included hematologic cytopenias associated with conditioning chemotherapy. There were no study discontinuations or deaths due to TEAEs other than one patient with stable disease who died on Day 38 due to sepsis not considered related to FT819 by the study investigator. The ASH presentation featured a patient case study demonstrating the potential to safely administer more than one treatment cycle of FT819 and reinduce an objective response following disease progression. The 73 year-old female with DLBCL had previously been treated with 4 prior lines of therapy, including commercial autologous CD19-targeted CAR T-cell therapy with best response of PR, and was refractory to last prior therapy. The patient received a first treatment cycle with a single dose of FT819 at 90 million cells, achieving a PR at Day 30 with 94% reduction in size of target lesions. Continued follow-up through November 8, 2022 was significant for disease progression on Day 72, for which the patient received a second treatment cycle with a single dose of FT819 at 180 million cells on Day 134 with consent from the U.S. Food and Drug Administration and achieved a PR at Day 163 with 61% reduction in size of target lesions. Both treatment cycles were well tolerated with no Grade 3 or greater FT819-related AEs or serious AEs, no reports of any grade of CRS, ICANS, or GvHD, and no evidence of new or worsening toxicity with the second treatment cycle. Following each treatment cycle, FT819 was detected in the peripheral blood with peak level at Day 4 in Cycle 1 and at Day 8 in Cycle 2, with maximum peak level at Day 8 in Cycle 2 at 8,152 transgene copies/undefined DNA. Dose escalation is currently ongoing in Regimen A as a single dose of FT819 at 360 million cells and in Regimen B with three fractionated doses at 60 million cells per dose. The Company has also amended the FT819 study protocol to allow for the use of bendamustine at 90 mg/m2 for 2 days as an alternative to Cy / Flu conditioning chemotherapy.

15:50 EST Kura Oncology presents updated clinical data from KOMET-001 trial - Kura Oncology announced updated clinical data from KOMET-001, a Phase 1/2 trial of the company's potent and selective menin inhibitor, ziftomenib, including an encouraging safety and tolerability profile and clinical activity in patients with relapsed/refractory acute myeloid leukemia . In the Phase 1a dose-escalation trial, ziftomenib demonstrated a wide therapeutic window and encouraging monotherapy activity in an all-comer population of 30 patients with relapsed/refractory AML, including a complete remission with no evidence of minimal residual disease in an NPM1-mutant patient with DNMT3A and KMT2D co-mutations. The patient entered the trial having progressed through seven prior lines of therapy and remains on ziftomenib after two years. In order to inform an optimal Phase 2 dose and in consultation with the U.S. Food and Drug Administration and its Project Optimus initiative, Kura conducted a Phase 1b trial with two randomized expansion cohorts, each comprised of NPM1-mutant and KMT2A-rearranged AML patients. A total of 53 patients were ultimately treated in the Phase 1b trial: 17 at 200 mg and 36 at 600 mg. These patients were heavily pretreated and received a median of three prior lines of therapy, with the majority of patients having received prior venetoclax and a quarter having progressed after at least one prior stem cell transplant. As of the data cutoff on October 24, 2022, 10 of the patients treated at 600 mg remained on ziftomenib and 17 were still in follow-up. Median duration of response has not been reached. Ziftomenib demonstrated optimal clinical benefit at 600 mg with a 30% CR rate in patients with NPM1-mutant AML, compared to 17% at 200 mg. Notably, four of the six NPM1-mutant patients who achieved a CR at 600 mg had IDH and/or FLT3 co-mutations. Overall, four of the seven patients with IDH co-mutations achieved a CR on ziftomenib. Of the five patients assessed for MRD at 600 mg, three were MRD negative. Although meaningful clinical benefit was observed in patients with KMT2A rearrangements, symptoms of differentiation syndrome prevented most patients from receiving sufficient therapy to attain response criteria for CR or CR with partial hematologic recovery, and only one patient achieved a CR/CRh. Continuous daily dosing of ziftomenib has been well tolerated. Reported adverse events most often were consistent with features of underlying disease. No evidence of drug-induced QTc prolongation was observed. Six patients discontinued due to adverse events; however, none of these were considered treatment related. Kura believes the higher incidence of DS observed in the KMT2A-rearranged patients is due to their much higher incidence of disease in extramedullary sites, induced to differentiate by the high tissue penetrance demonstrated by ziftomenib preclinically. By combining ziftomenib with appropriate standards of care, the Company believes it can reduce this extramedullary disease burden and consequent DS symptoms, keep patients on ziftomenib therapy longer and drive superior treatment outcomes in patients with KMT2A-rearranged AML.

15:45 EST Fate presents interim clinical data from ongoing Phase 1 stuty of FT576 - Fate Therapeutics presented interim clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT576 for patients with relapsed / refractory multiple myeloma at the 64th American Society of Hematology Annual Meeting and Exposition. The off-the-shelf product candidate, which is derived from a clonal master engineered induced pluripotent stem cell line, incorporates a chimeric antigen receptor targeting B-cell maturation antigen as well as a high-affinity, non-cleavable CD16 Fc receptor to maximize antibody-dependent cellular cytotoxicity and enable dual-antigen targeting of myeloma cells through combination with monoclonal antibody therapy. Preclinical data published last month in the journal Nature Communications demonstrated that single-dose administration of FT576 was effective at controlling tumor growth in vivo, with deeper and more sustained anti-tumor activity observed through multi-dose administration of FT576 as well as in combination with the CD38-targeted monoclonal antibody daratumumab. The multi-center Phase 1 clinical trial of FT576 is designed to assess its safety and clinical activity in adult patients with r/r MM, and to determine the recommended Phase 2 dose and schedule, as monotherapy and in combination with daratumumab to simultaneously target BCMA and CD38. As of the October 7, 2022 data cutoff date, 9 patients with r/r MM have been treated with a single dose of FT576, including 6 patients in Regimen A and 3 patients in Regimen B. Patients received standard conditioning chemotherapy consisting of cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m2 for 3 days prior to the initiation of each regimen. Patients were heavily pre-treated having received a median of 5 prior lines of therapy, including 6 patients that were refractory to last therapy. In Regimen A, 6 patients were treated with a single dose of FT576 as monotherapy in the first dose cohort at 100 million cells and the second dose cohort at 300 million cells. In the second dose cohort, one patient, who had received 5 prior lines of therapy, was triple-refractory to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 mAb, and was refractory to last therapy, achieved a very good partial response with the other two patients showing stable disease. Further evidence of FT576 activity was observed in the second dose cohort, with two patients for whom serum BCMA levels were evaluable showing a substantial treatment-induced decrease in soluble BCMA. In Regimen B, 3 patients were treated with a single dose of FT576 in combination with daratumumab in the first dose cohort at 100 million cells, with one patient achieving a partial response and one patient achieving a minor response. All 3 patients showed a substantial treatment-induced decrease in soluble BCMA. The company has now initiated enrollment of two-dose escalation cohorts at 300 million cells per dose in both regimens. No dose-limiting toxicities, and no events of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. Both FT576 treatment regimens were well tolerated. Two patients experienced Grade 3 or greater FT576-related adverse events (AEs), with one patient having Grade 3 diarrhea and one patient having two episodes of Grades 3 through 4 neutropenia and 3 episodes of Grade 3 anemia, all of which resolved. There were no serious AEs related to FT576. Grade 3 or greater treatment-emergent AEs not related to FT576 primarily included hematologic cytopenias associated with conditioning chemotherapy. There were no study discontinuations or deaths due to TEAEs. Under its collaboration with Janssen Biotech, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (JNJ), the company is currently conducting preclinical development of FT555, a multiplexed-engineered CAR NK cell product candidate derived from a clonal master engineered iPSC line incorporating four functional components: a proprietary CAR optimized for NK cell biology that targets GPRC5D, an orphan G-protein-coupled receptor expressed on myeloma cells with a distribution that is similar to but independent of BCMA; a novel hnCD16 Fc receptor for enhanced ADCC; an IL-15 receptor fusion that augments NK cell activity; and the deletion of the CD38 gene, which promotes persistence and function in high oxidative stress environments. At ASH, scientists from the companies jointly presented preclinical data demonstrating that single-dose administration of FT555 as monotherapy resulted in robust and durable antigen-mediated tumor regression in two independent disseminated tumor models of aggressive myeloma, which activity was further improved in combination with daratumumab to simultaneously target GPRC5D and CD38 antigens. Administration of three doses of FT555 as monotherapy further improved tumor clearance and showed superior activity compared to single-dose primary CAR T cells.

15:39 EST Centessa announces additional data OLE of Phase 2a SerpinPC study - Centessa Pharmaceuticals announced new data from an additional 18-months of continued treatment with SerpinPC, an investigational, subcutaneously administered novel inhibitor of activated protein C, from the open-label extension, or OLE, of the Phase 2a study of SerpinPC for hemophilia. The OLE data were shared today in an oral presentation at the American Society of Hematology Annual Meeting. The OLE data show a continued favorable safety and tolerability profile for SerpinPC, including at a higher dosing regimen, as well as sustained long-term efficacy results, as measured by a reduction in the all-bleeds annualized bleed rates. Consistent with data from the six-month repeat dose portion of the Phase 2a study, there were no thromboembolic events and no treatment-related sustained elevations of D-dimer observed throughout the 18-month OLE period reported on today. D-dimer is a sensitive measure of excess thrombin generation. In addition, there were no SerpinPC-related adverse events during the OLE period.

15:33 EST IGM Biosciences presents data from T cell engager portfolio - IGM Biosciences announced the presentation of data from IGM's expanding portfolio of T cell engagers for hematologic malignancies, including IGM-2644, IGM-2537 and imvotamab, at the 2022 American Society of Hematology Annual Meeting and Exposition being held virtually and in-person in New Orleans, Louisiana, December 10-13, 2022. "As shown today, the preclinical profiles of IGM-2644, our CD38 x CD3 bispecific IgM antibody, and IGM-2537, our CD123 x CD3 bispecific IgM antibody, demonstrate the potential for encouraging antitumor activity coupled with favorable safety profiles," said Chris Takimoto, Chief Medical Officer of IGM Biosciences. "We are also presenting today biomarker data from the Phase 1 trial of imvotamab, our CD20 x CD3 bispecific IgM antibody, showing its encouraging activity in patients with low CD20 expressing tumors." The poster titled "IGM-2644, a Novel CD38 x CD3 Bispecific IgM T Cell Engager Demonstrates Potent Efficacy on Myeloma Cells with an Improved Preclinical Safety Profile" highlights IGM-2644's greater complement dependent cytotoxicity activity as compared to conventional IgG anti-CD38 antibodies. Additionally, IGM-2644 achieved potent T cell dependent cellular cytotoxicity killing of daratumumab-resistant cell lines with minimal cytokine release as well as potent TDCC killing of myeloma patient samples. IGM-2644 was also shown to inhibit CD38+ tumor growth in humanized xenograft models, but it avoids killing immune effector cells as compared to an IgG bispecific T cell engager. IGM plans to initiate a Phase 1 trial of IGM-2644 in multiple myeloma in the first quarter of 2023, subject to Investigational New Drug application clearance. The poster titled "CD123 Directed IgM T-cell Engager, IGM-2537, Demonstrates Potent in vitro and in vivo Activity with Minimal Cytokine Release" highlights potent in vitro and in vivo activity with limited cytokine induction consistent with the potential for providing a favorable safety profile for a CD123-directed IgM-based T cell engager. IGM-2537 was shown to bind to human CD123 with high affinity, avidity, and specificity. IGM-2537 co-engaged with both CD123 and CD3 antigens, leading to T cell redirected killing of acute myeloid leukemia cell lines with concomitant T cell activation, and eliminated AML blast cells at physiologically relevant effector/target ratios in an ex vivo assay. IGM-2537 also showed significantly reduced cytokine release, exemplified by IFN-gamma, TNF-alpha and IL-6, as compared to an IgG T cell engager molecule. IGM expects to file an IND application for IGM-2537 in AML in 2023. The poster titled "Pharmacodynamics and Biomarker Correlates of Imvotamab (IGM-2323), the First-in-Class CD20xCD3 Bispecific IgM Antibody with Dual Mechanisms of Action, in Patients with Advanced B Cell Malignancies" features biomarker data from the Phase 1 trial evaluating imvotamab, the Company's IgM T cell engaging bispecific antibody. The poster highlights that complete responses were observed even in patients with low CD20 expressing tumors. Biomarker data obtained from patients in dose escalation cohorts also demonstrated pharmacodynamic changes that support the TDCC and CDC mechanisms of action of imvotamab.

15:29 EST Kronos presents preclinical data supporting lanraplenib anti-leukemic activity - Kronos Bio presented preclinical data that demonstrate anti-leukemic activity of the investigational spleen tyrosine kinase inhibitor, lanraplenib, in combination with multiple targeted agents in patient-derived cell isolates and cell lines at the 64th American Society of Hematology Annual Meeting & Exposition in New Orleans. Lanraplenib is a next-generation SYK inhibitor that is currently being evaluated in combination with gilteritinib in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia in a Phase 1b/2 study. The company anticipates sharing initial data from the lanraplenib/gilteritinib trial, along with the recommended Phase 2 dose, in the fourth quarter of 2023 or first quarter of 2024. Researchers evaluated lanraplenib and a second SYK inhibitor, entospletinib, which the company has discontinued developing, in combination with a menin inhibitor, in two cell lines with FLT3 internal tandem duplication/MLL rearrangement. Synergistic anti-proliferative effects were observed across a broad range of concentrations. The combination triggered differentiation and apoptosis, suggesting a more complete blockade of the HOXA9/MEIS1 transcriptional program through synergistic inhibition by orthogonal mechanisms. Additionally, the researchers evaluated synergistic activity of lanraplenib with the FLT3 inhibitor, gilteritinib, and BCL2 inhibitor, venetoclax, in patient-derived AML isolates. This analysis found synergistic anti-proliferative activity for both combinations. Patient-derived xenograft studies also demonstrated deeper reductions in leukemic burden in the peripheral blood and bone marrow after 28 days of treatment with lanraplenib and gilteritinib. In a follow-up PDX study with an optimized regimen, the combination significantly extended overall survival compared to either single agent. Kronos Bio also presented two posters at the meeting focused on increasing the understanding of measurable residual disease negative CR as a surrogate endpoint in AML trials. One poster analyzed MRD and survival data from 1,128 patients with NPM1-mutated AML in three cooperative group trials, confirming that achieving MRD negative CR predicts better overall and event-free survival. A second poster described the development of a next generation sequencing-based assay for measuring MRD and compared the performance of this assay against the gold standard RT-qPCR based method.

15:20 EST Aptose Biosciences provides clinical update on tuspetinib, luxeptinib - Aptose Biosciences has provided a clinical update of its lead oral myeloid kinome inhibitor, tuspetinib, as responses continue to emerge from a Phase 1/2 trial, and from its oral, dual lymphoid and myeloid kinase inhibitor, luxeptinib in an ongoing Phase 1a/b trial. Tuspetinib, a once daily oral agent designed to target FLT3, SYK, and JAK kinases but avoid targets that drive toxicities, safely delivered complete remissions as a monotherapy across four dose levels in acute myeloid leukemia patients that previously had been failed by chemotherapy, Bcl-2 inhibitors, hypomethylating agents, competitor FLT3 inhibitors, and hematopoietic stem cell transplants. Data are being presented at the 2022 American Society of Hematology annual meeting, showing tuspetinib delivers single agent responses in very ill and heavily pretreated relapsed or refractory AML patients of mutationally-defined populations, including those with AML harboring wild-type FLT3, ITD or TKD mutated FLT3, or mutated forms of NPM1, MLL,TP53, NRAS, KRAS, DNMT3A, RUNX1, various slicing factors, and other genes. As of October 6, 2022, 60 heavily pretreated relapsed/refractory AML patients were enrolled at multiple centers and treated at doses escalating from 20 mg to 200 mg, with further dose exploration at the 40 mg, 80 mg, 120 mg and 160 mg dose levels. Prior to Aptose licensing tuspetinib, Hanmi Pharmaceutical Company demonstrated complete remissions at the 80 mg dose level. As of January 1, 2022, Aptose assumed control of clinical trial activities and has demonstrated additional complete remissions at the 120 mg, 160 mg, and now the 40 mg dose levels. Many responders were bridged successfully to hematopoietic stem cell transplant, while others not eligible for HSCT remained on tuspetinib with a durable response and no drug related myelosuppression even after months of continuous dosing. The noteworthy safety and potency profile position tuspetinib, in both FLT3 mutated and wildtype AML patients, potentially to become the kinase inhibitor of choice to combine with venetoclax and hypomethylating agents to deliver high response rates without exacerbated myelosuppression or life-threatening toxicities and potentially to become the preferred agent for maintenance therapy to prevent relapse after HSCT or drug-induced complete remissions. Such roles can define the ultimate therapeutic success for patients and commercial success for tuspetinib. For the APTIVATE expansion trial that has initiated patient enrollment, Aptose has selected 120 mg as the initiating single agent expansion dose and 80 mg as the initiating dose selected for combination with venetoclax. The trial is designed to confirm activity through patient enrichment of specific mutationally defined AML populations, including FLT3-mutant patients who have been failed by a prior FLT3 inhibitor, as supported by fast-track designation and a significant response rate to date. Aptose also provided an update of the luxeptinib clinical program. Luxeptinib is an oral, first-in-class FLT3 and BTK kinase inhibitor in Phase 1 a/b clinical studies for the treatment of myeloid hematologic malignancies. This small molecule demonstrates potent inhibition of wild type and all mutant forms of FLT3 and cures animals of AML in the absence of toxicity in murine leukemia models. Just recently, a CR was achieved with a diffuse large B-cell lymphoma patient at the end of Cycle 22 with 900mg BID of the original G1 formulation. Previously, an MRD-negative CR was reported with a R/R AML patient receiving 450mg BID of the original G1 formulation. Collectively, these findings demonstrate luxeptinib is active against AML as well as lymphoid malignancies. The original G1 formulation of luxeptinib was hampered by poor absorption. The new "G3" formulation was designed and developed for more rapid absorption, more efficient absorption, longer retention, and greater accumulation. The new G3 formulation this year was tested as a single dose in 20 patients from a Phase 1 clinical program of luxeptinib. Modeling of the pharmacokinetic properties of G3 predicts steady-state plasma exposure from continuous dosing with 50 mg of G3 should be comparable to that of 900 mg of the original G1 formulation Q12h, representing up to an 18-fold improvement in bioavailability with G3. Aptose recently announced dosing of the first patient with continuous dosing of the G3 formulation in an ongoing Phase 1a/b clinical trial in patients with relapsed or refractory AML. A second patient now has initiated continuous dosing with the G3 formulation. The G3 formulation may result in greater exposures of luxeptinib and additional responses in these difficult-to-treat patient populations. Aptose expects that 9-15 patients will determine if G3 is safe and achieves desired exposures to deliver clinical responses.

15:08 EST Roche announces new data from Phase 3 COMMODORE 3 study in China - Roche announced new data from the phase III COMMODORE 3 study in China, demonstrating that crovalimab, a novel anti-C5 recycling monoclonal antibody, is efficacious and well-tolerated in people with paroxysmal nocturnal haemoglobinuria. The study met its co-primary efficacy endpoints of transfusion avoidance and haemolysis control, demonstrating that participants with PNH, who have not been treated previously with complement inhibitors and who received subcutaneous crovalimab injections every four weeks, achieved disease control.The data were presented at the American Society of Hematology congress, taking place from 10-13 December 2022." The COMMODORE 3 study included data from 51 participants with PNH, who received crovalimab subcutaneously every four weeks during the primary study period. Results showed that the co-primary efficacy endpoints of haemolysis control and TA, indicators of disease control, were met. The mean proportion of participants with haemolysis control from week five through to week 25 was 78.7%. The difference between the proportion of participants with TA within 24 weeks prior to screening and the proportion of participants with TA from baseline through to week 25 was statistically significant. TA is defined as people who become transfusion-free and do not require transfusion per protocol-specified guidelines. Blood transfusion requirements are important clinical measures of haemolysis caused by complement dysregulation in PNH. In addition, the proportion of participants with breakthrough haemolysis from baseline through week 25 was 3.9%, and the proportion of participants who achieved haemoglobin stabilisation was 51%. A rapid and clinically meaningful improvement in fatigue status within two weeks after treatment with crovalimab was also reported and sustained over time, as measured by the FACIT-Fatigue scale. The overall safety data were consistent with the known safety profile of C5 inhibitors and underlying disease, showing that crovalimab was well-tolerated with no new safety signals identified. Data from the COMMODORE 3 study have been submitted via China's Centre for Drug Evaluation Breakthrough Therapy Designation pathway. This submission has been accepted under Priority Review for approval consideration in PNH by China's National Medical Products Administration. As the availability of C5 inhibitors is extremely limited in China, there remains a high clinical need for people living with PNH there. Data from the global crovalimab COMMODORE 1 and COMMODORE 2 PNH studies are expected in 2023. Crovalimab is being investigated as a potential treatment option for people living with PNH and other diseases such as atypical haemolytic uraemic syndrome and sickle cell disease.