On December 9, 2019 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported an update of preliminary data from the MANIFEST clinical trial in oral and poster presentations at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando (Press release, Constellation Pharmaceuticals, DEC 9, 2019, View Source [SID1234552110]).

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MANIFEST is an open-label Phase 2 clinical trial of the Company’s bromodomain and extra-terminal domain (BET) protein inhibitor CPI-0610 in patients with myelofibrosis (MF). Arm 3 is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients. Arms 1 and 2 are studying CPI-0610 as a monotherapy or in combination with ruxolitinib in ruxolitinib-resistant or -intolerant MF patients.

The updated preliminary data presented at ASH (Free ASH Whitepaper) showed signs of clinical activity for CPI-0610 similar to that previously reported at the annual meetings of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Hematology Association (EHA) (Free EHA Whitepaper) and in the ASH (Free ASH Whitepaper) abstracts. The preliminary data included data on additional patients and showed evidence of activity across a broad range of myelofibrosis parameters in both JAK-inhibitor-naïve and ruxolitinib-resistant or -intolerant patients.

"If trends in preliminary data from MANIFEST in JAK-inhibitor-naïve patients are confirmed with further study, CPI-0610 has the potential to transform the standard of care in these patients," said Claire Harrison, D.M., Professor of Haematology, and Clinical Director, Guy’s and St Thomas’ NHS Foundation Trust, and a MANIFEST investigator.

"Preliminary data from MANIFEST in ruxolitinib-resistant or -intolerant patients are encouraging, suggesting the potential opportunity for a differentiated treatment option in such patients," said John Mascarenhas, M.D., Associate Professor, the Icahn School of Medicine at Mount Sinai, and a MANIFEST investigator.

The presentations at ASH (Free ASH Whitepaper) reflect data as of an October 17, 2019, data cutoff, updating preliminary data presented in ASH (Free ASH Whitepaper) abstracts published on November 6, 2019, as of a June 27, 2019, data cutoff.

Below are highlights of the presentations at ASH (Free ASH Whitepaper):

JAK-Inhibitor-Naïve Patients (Arm 3)

SVR35: Twelve out of 15 (80%) evaluable JAK-inhibitor-naïve patients experienced SVR35 at 12 weeks. The median percent change in spleen volume reduction was -49.7%.
TSS50: Ten out of 14 (71%) evaluable patients achieved at least a 50% improvement in Total Symptom Score (TSS50) at 12 weeks. The median percent change in TSS at 12 weeks was -60.3%.
Ruxolitinib-Resistant or -Intolerant Patients (Arms 1 and 2)

CPI-0610 Add-on to Ruxolitinib in Transfusion-Dependent Patients (Cohort 2A)

SVR35: At 24 weeks, SVR35 was achieved in 3 out of 12 (25%) evaluable patients, with a median percent change of -24.9%. An SVR35 at any time (best response) was achieved in 5 out of 17 (29%) evaluable patients, with a best median percent change of -21.2%.
SVR: At 24 weeks, 11 out of 12 (92%) evaluable patients had a spleen volume reduction.
TSS50: At 24 weeks, TSS50 was achieved in 7 out of 13 (54%) evaluable patients, with a median percent change of -58.8%. A TSS50 at any time (best response) was achieved in 13 out of 17 (76.5%) evaluable patients, with a median best change of -71.0%.
TD to TI: Conversion from transfusion dependence (TD) to transfusion independence (TI) occurred in 6 out of 14 (43%) evaluable patients with at least 24 weeks of treatment.
Other Ruxolitinib-Resistant or -Intolerant Patients (Cohorts 1A, 1B, and 2B)

SVR35: None of the patients in these cohorts achieved SVR35 at 24 weeks. An SVR35 at any time (best response) was achieved in 1 out of 4 evaluable patients in cohort 1A.
SVR: Nine out of 13 (69%) evaluable patients in Cohort 2B, 1 out of 2 (50%) evaluable patients in Cohort 1A, and 5 out of 7 (71%) evaluable patients in Cohort 1B achieved a spleen volume reduction at 24 weeks. The median reductions were -10.9%, -3.2%, and -26.0%, respectively.
TSS50: Five out of 13 (38%) evaluable patients in Cohort 2B, 0 out of 1 evaluable patient in Cohort 1A, and 3 out of 5 (60%) evaluable patients in Cohort 1B achieved a TSS50 at 24 weeks. Median reductions were -44.1%, -18.4%, and -53.5%, respectively.
TD to TI: Zero out of 2 TD patients in cohort 1A with at least 24 weeks of treatment converted to TI.
Additional Data Supporting Possible Disease Modification

Hemoglobin Improvement: Six out of 11 (55%) evaluable patients treated with CPI-0610 monotherapy and 2 out of 15 (13%) evaluable patients treated with CPI-0610 + ruxolitinib achieved at least a 1.5 g/dL improvement in hemoglobin without receiving a blood transfusion in the 12 weeks prior to assessment.
Bone Marrow Fibrosis Score Improvement: Twelve out of 32 (38%) evaluable patients in Arms 1 and 2, including 7 out 11 (63%) evaluable patients in Cohort 2A, achieved at least a one-grade improvement in bone marrow fibrosis score. Ten out of 12 improvements occurred within the first six months of treatment.
Safety

CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve patients (Arm 3) was generally well tolerated. No adverse events led to study discontinuation. Three patients (10%) had ≥ Grade 3 anemia. One patient (3.3%) had Grade 4 thrombocytopenia, which was reversible. The most common non-hematologic adverse events were diarrhea, nausea, dizziness, and muscle spasms, which were primarily Grade 1/2.
CPI-0610 as monotherapy or in combination with ruxolitinib in ruxolitinib-refractory or -intolerant patients (Arms 1 and 2) was generally well tolerated. The most common hematologic adverse event was thrombocytopenia. Nine patients (10%) had ≥ Grade 3 thrombocytopenia, none of which were serious adverse events. These nine patients included two (5.6%) in Arm 1 and seven (12.9%) in Arm 2. The most common non-hematologic adverse events, primarily Grade 1/2, were diarrhea, nausea, cough, fatigue, vomiting, and upper respiratory tract infection. Eight out of 90 (8.9%) patients reported Grade 4 adverse events, all of which resolved. Of these eight, four (11.1%) occurred in Arm 1, of which three required dose interruption and one (rash) was considered related to CPI-0610, and four (7.4%) occurred in Arm 2, none required dose reduction and one (anemia) was considered related to the combination therapy. One ruxolitinib-resistant or -intolerant patient (1.1%) discontinued due to serious adverse event(s), which were reported as unlikely to have been related to CPI-0610. Three out of 90 (3.3%) ruxolitinib-resistant or -intolerant patients, all in Arm 2, reported Grade 5 adverse events—acute kidney injury, traumatic subdural hematoma (fall due to tripping), and brain stem hemorrhage (no concomitant thrombocytopenia)—none of which were considered by Constellation to be related to CPI-0610.
Orphan Drug Designation

The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to CPI-0610 for the treatment of MF on November 20, 2019.
The FDA Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Under specified conditions, this designation may provide companies a seven-year marketing exclusivity period, as well as certain incentives, including federal grants, tax credits, and a waiver of Prescription Drug User Fee Act (PDUFA) filing fees.
Future Plans

Constellation continues to enroll patients in MANIFEST. As a result of encouraging preliminary data, Constellation expanded Arm 3 of MANIFEST for JAK-inhibitor-naïve patients from 43 to up to 101 patients. The Company also expanded Cohort 2A, for TD ruxolitinib-resistant or -intolerant patients adding CPI-0610 to ruxolitinib, from 16 to up to 60 patients.
Constellation has started planning for a randomized, active-controlled, pivotal Phase 3 clinical trial studying the combination of CPI-0610 and ruxolitinib versus ruxolitinib and placebo in JAK-inhibitor-naïve patients with MF. The Company expects this clinical trial to start in 2020.
Investor Event

Constellation will host an analyst/investor event and webcast today at 12:30 PM EST in Salon 2 at the Rosen Centre Hotel in Orlando in conjunction with the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at View Source Analysts and investors may also access the event and participate in the live question-and-answer session by dialing (877) 473-2077 (domestic) or (661) 378-9662 (international) and referring to conference ID 7892044. A replay of the call will be available at (855) 859-2056, (404) 537-3406, or (800) 585-8367.
About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

On December 9, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the presentation of fractionated dosing data in 19 patients with relapsed/refractory multiple myeloma (Press release, Cellectar Biosciences, DEC 9, 2019, View Source [SID1234552109]). Dr. Sikander Ailawadhi, M.D., Associate Professor, Division of Hematology/Oncology at Mayo Clinic Florida, presented the data in an oral presentation at the 61st Annual American Society of Hematology (ASH) (Free ASH Whitepaper) meeting.

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Dr. Ailawadhi’s presentation highlighted results from 19 patients with relapsed/refractory multiple myeloma from Cellectar’s Phase 1 and Phase 2 CLOVER-1 trial collected prior to July 30, 2019. The data from the oral presentation support prior literature and preclinical data showing that fractionated dosing provides an enhancement of efficacy and safety while reducing adverse events. The patients presented received one of 3 dose levels: a single bolus dose of 31.25 mCi/m2 or a fractionated dose of 31.25 mCi/m2 or a higher fractionated dose of 37.5 mCi/m2 of CLR 131. The fractionated 37.5 mCi/m2 dose of CLR 131 represents the greatest amount of drug administered to date in the Phase 2 CLOVER-1 trial. The overall response rate (ORR) for all multiple myeloma patients across the 3 dose cohorts was 31.3% and a 100% disease control rate. Patients receiving the higher fractionated 37.5 mCi/m2 dose demonstrated a 50% ORR with the remaining 50% having minimal responses (greater than a 25% reduction in the surrogate marker of efficacy).

The patients presented had received a median of 4 prior systemic therapies (range 2-13), had a median age of 69 (range 51-83), including 8 females and 11 males and 80% of the patients in the 37.5 mCi/m2 cohort were either quad or penta-refractory, and all were refractory to daratumumab.

"These data showing a 50% overall response rate in a cohort of heavily pretreated multiple myeloma patients and a 31.3% overall response rate in all dose levels presented is impressive," said Dr. Ailawadhi. "CLR 131 continued to demonstrate a good safety profile with limited off-target effects and the fractionated dosing of CLR 131 showed improved tolerability versus single bolus dosing. While these doses demonstrate beneficial activity, there is the potential that a second cycle or further fractionation could further enhance both efficacy and tolerability."

The primary adverse events (AEs) at all dosing levels were cytopenias and included thrombocytopenia, anemia, and neutropenia. The hematologic AEs were expected, manageable and followed a predictable timeline to nadir (average 40 days) and subsequent recovery (average 17 days post nadir). The demonstrated recovery post nadir for CLR 131 compared favorably to other similar radiotherapeutic drugs, such as Bexxar, which requires on average 90 days for recovery post nadir.

"These results showed excellent safety with limited off-target effects and improved tolerability compared to our single bolus dosing. With the overall activity observed with CLR 131 to date and efficacy signals across all doses and especially at the fractionated dosing level of 37.5 mCi/m2, we remain optimistic about the potential for continued enhancement of efficacy and safety with fractionated dosing," said Jim Caruso, president and CEO of Cellectar. "We anticipate announcing additional data in the coming weeks in patients receiving single bolus and fractionated dosing from our Phase 2 CLOVER-1 trial, in which we have enrolled approximately 50 patients."

About the Phase 2 CLOVER-1 Trial

CLOVER-1 is a Phase 2 study of CLR 131 being conducted in approximately 10 leading cancer centers in the United States in patients with relapsed or refractory B-cell hematologic cancers. The hematologic cancers being studied in the trial include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

The study will enroll up to 80 patients. Its primary endpoint is clinical benefit response (CBR), with additional endpoints of overall response rate (ORR), progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a fractionated dose of 37.5mCi/m2 of CLR 131 administered in two 30-minute infusions of 18.75mCi/m2 of CLR 131 administered on day 1 and day 7 (± 1), with the option for a second dose cycle approximately 75-180 days later. The company expects to report topline data in 2019.

Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the trial. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About the Phase 1 R/R MM Trial

The Phase 1 multicenter, open-label, dose-escalation study is designed to evaluate the safety and tolerability of CLR 131 administered as a 30-minute IV infusion, either as a single bolus dose or as two fractionated doses, in patients with R/R MM. All doses to date have been deemed safe and well tolerated by an independent Data Monitoring Committee (DMC). Based on the data and the recommendation of the DMC, the Company is enrolling a Cohort 7 where patients will receive 40mCi/m2 fractionated dose of CLR 131.

About CLR 131

CLR 131 is a small-molecule, targeted Phospholipid Drug Conjugate (PDC) designed to deliver cytotoxic radiation directly to cancer cells, while limiting exposure to healthy cells. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-cell lymphomas, and two Phase 1 dose-escalating clinical studies, one in multiple myeloma and one in pediatric solid tumors and lymphoma. CLR 131 was granted Orphan Drug designation for the treatment of multiple myeloma by both the U.S. and the European Commission, and was granted U.S. Orphan Drug and Rare Pediatric Disease designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

On December 9, 2019 bluebird bio, Inc. (Nasdaq: BLUE) and Bristol-Myers Squibb (NYSE: BMY) reported that updated safety and efficacy results from the ongoing Phase 1 study (CRB-402) of bb21217, an investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy being studied in patients with relapsed/refractory multiple myeloma (R/RMM) (Press release, Bristol-Myers Squibb, DEC 9, 2019, View Source [SID1234552108]). The data were presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida.

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bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the idecabtagene vicleucel (ide-cel; bb2121) CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention to increase the in vivo persistence of CAR T cells.

"Early data from the CRB-402 study in heavily pre-treated patients (median of six prior lines) with relapsed/refractory multiple myeloma demonstrate the potential for durable responses following bb21217 CAR T cell treatment, with a median duration of response of 11.1 months at the 150 x 106 CAR+ T cell dose level," said David Davidson, M.D., chief medical officer, bluebird bio. "Consistent with the hypothesis underlying the bb21217 program that memory-like phenotype T cells may survive longer in vivo, we have observed durable CAR T cell persistence in evaluable patients (n=2/2) with ongoing response at up to 18 months following treatment. We are continuing to recruit additional patients in the study and performing ongoing assessments of the functional persistence of bb21217, as well as its potential correlation to durability of response."

CRB-402, the first in-human study of bb21217 in patients with R/RMM, is designed to assess the primary endpoint of safety as well as other pre-defined endpoints including efficacy and pharmacokinetics measurements. CRB-402 is a two-part, open-label, multi-site Phase 1 study of bb21217 in adults with R/RMM with a projected final enrollment of 74 patients. The dose escalation part of CRB-402 is complete, and the dose expansion part of the study is ongoing.

"The data of CRB-402 provide additional support that targeting BCMA with a CAR T therapy could be beneficial in treating relapsed/refractory multiple myeloma, particularly for heavily pre-treated patients," said Kristen Hege, M.D., Senior Vice President, Hematology/Oncology and Cell Therapy, Early Clinical Development for Bristol-Myers Squibb. "We have observed durable responses with bb21217 in this study and look forward to further results."

"One of the challenges in treating patients with relapsed/refractory multiple myeloma is that they often become resistant to currently available therapies and response durations generally shorten with each subsequent therapy," said presenting author Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood Cancers, Nashville, Tennessee. "In this heavily-treated patient population, we are encouraged by the results with bb21217 treatment in this ongoing study."

As of the September 4, 2019 cutoff date, data include results for 38 treated patients. Twenty-four patients received bb21217 in the dose escalation cohort at three dose levels (12 at 150 x 106 CAR+ T cells; six at 300 x 106 CAR+ T cells; and six at 450 x 106 CAR+ T cells). Fourteen additional patients received bb21217 in the dose expansion cohort at two dose levels (8 at 300 x 106 CAR+ T cells and 6 at 450 x 106 CAR+ T cells). The patients had a median of six prior lines of therapy (min – max; 3 – 17 lines) and 82% had at least one prior autologous stem cell transplant. High-risk cytogenetics were reported in 34% of patients and 95% of patients received prior treatment with an anti-CD38 antibody. All patients treated in CRB-402 (n=38) had previously received at least three prior lines of therapy, including an immunomodulatory agent and proteasome inhibitor. The enrollment criteria for the dose expansion cohort required all enrolled patients (n=14) to be refractory to their last prior line of therapy and have previously received an anti-CD38 antibody.

Safety Results
As of the data cutoff, the adverse events observed with bb21217 were consistent with known toxicities of CAR T therapies, regardless of dose level.

Of the 38 treated patients, the most common Grade 3/4 toxicities include neutropenia (82%), leukopenia (55%), thrombocytopenia (55%), anemia (50%), lymphopenia (34%), hypophosphatemia (21%), hyponatremia (13%) and febrile neutropenia (11%). Grade 3/4 infections were reported in seven patients (18%).

Twenty-five of 38 patients (66%) developed bb21217-related cytokine release syndrome (CRS); 12 Grade 1, 11 Grade 2, one Grade 3 and one Grade 5 (death). The fatal CRS event occurred at the 450 x 106 CAR+ T cells dose level, after 15 days of follow-up. Nine of 38 (24%) patients developed neurotoxicity; three Grade 1, three Grade 2, two Grade 3 (one with vertigo/dizziness and one with encephalopathy) and one Grade 4 (encephalopathy, previously reported). For the one patient previously reported with Grade 4 neurotoxicity, Grade 3 CRS was also reported, and both have resolved.

Efficacy Results
As of the data cutoff, 33 of the 38 patients were evaluable for clinical response as defined per the International Myeloma Working Group Uniform Response Criteria for multiple myeloma.

Twelve patients were evaluable in the 150 x 106 CAR+ T cells cohort, with a median follow-up of 17.6 months (min – max; 12 – 23 months). Ten of 12 (83%) evaluable patients (defined as treated patients with ≥ two months of response data or progressive disease/death/lost to follow-up within <=2 months) in the 150 x 106 CAR+ T cells cohort demonstrated clinical response, including four with a stringent complete response (sCR) or complete response (CR), and six with a very good partial response (VGPR). Among the ten confirmed responders, the median duration of response was 11.1 months (95% Confidence Interval (CI); 3.3 – not estimable).

As of the data cutoff, follow-up within the two higher dose cohorts (300 x 106 and 450 x 106 CAR+ T cells) remains early and none of the confirmed responders have experienced disease progression. In the 300 x 106 CAR+ T cells cohort, 14 patients were evaluable for response and six of the 14 (43%) evaluable patients demonstrated clinical response, including four with a VGPR and two with a partial response (PR), with a median follow-up of four months (min – max; 2 – 10 months). In the 450 x 106 CAR+ T cells cohort, seven patients were evaluable for response and four of the seven (57%) evaluable patients demonstrated clinical response, including one with a sCR, two with a VGPR and one with a PR, with a median follow-up of 3.3 months (min – max; <1 – 6 months).

Evidence of myeloma in the bone marrow, known as minimal residual disease (MRD), was undetectable by next-generation sequencing at a sensitivity level of 10-5 in 94% (n=16/17) of all confirmed responders who had evaluable bone marrow samples (patients with > PR and > 1 valid post-baseline MRD assessment).

As of the data cutoff, CAR T cell persistence was observed in eight of ten patients with ongoing response and evaluable at six months, and two out of two patients with ongoing response and evaluable at 18 months.

The dose expansion part of the CRB-402 study is ongoing to further recruit patients and explore bb21217 at the 450 x 106 CAR+ T cells dose cohort, assess functional persistence of bb21217 and durability of response.

About bb21217 for Multiple Myeloma
bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention to increase the in vivo persistence of CAR T cells bb21217 is being developed in partnership between bluebird bio and Bristol-Myers Squibb.

The clinical development program for bb21217 includes the ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study of bb21217 in patients with R/RMM, designed to assess safety, pharmacokinetics, efficacy and duration of effect. CRB-402 is a two-part (completed dose escalation and ongoing dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with R/RMM with a projected final enrollment of 74 patients. For more information visit: clinicaltrials.gov using identifier NCT03274219.

bb21217 is not approved for any indication in any geography.

About Multiple Myeloma
Multiple myeloma is a cancer of certain cells in the blood, called plasma cells. The cause of multiple myeloma is not known, and currently there is no cure. However, there are a number of treatment options available that can lead to response. For some people with multiple myeloma, response can last many years. Patients who have already been treated with some available therapies but continue to have progression of their disease have "relapsed" and "refractory" multiple myeloma, meaning their cancer has reoccurred after they have received initial treatments. Patients with relapsed and refractory multiple myeloma have fewer treatment options.

On December 9, 2019 Avid Bioservices, Inc. (NASDAQ:CDMO) (NASDAQ:CDMOP), a dedicated biologics contract development and manufacturing organization (CDMO) working to improve patient lives by providing high quality development and manufacturing services to biotechnology and pharmaceutical companies, reported financial results for the second quarter of fiscal 2020 ended October 31, 2019 (Press release, Avid Bioservices, DEC 9, 2019, View Source [SID1234552106]).

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Highlights Since July 31, 2019

"During the second quarter of 2020, we strengthened multiple core areas of our business," said Rick Hancock, interim president and chief executive officer of Avid. "Our business development effort continues to be wide reaching and robust. Our reputation in the industry for quality and regulatory success continues to grow allowing us to engage with a broadening pool of potential new customers and expand our relationships with existing customers.

"Operationally, we continue to improve and enhance our equipment, facilities and systems. The opening of our new process development lab, the successful completion of our annual maintenance overhaul, and the planned installation of a new pharmaceutical grade water system in calendar 2020 all reflect the dedication we have to maintaining the highest standards possible.

"The revenues for this quarter were the highest since Avid transitioned to a pure-play CDMO in January 2018, and we achieved 18% gross margin, which represents a significant increase year-over-year as well as quarter-over-quarter. Expenses remained in line with expectations and our backlog continues to be strong. Also important, during the quarter we approached breakeven income from operations.

"Productivity and efficiency contributed significantly to Avid’s strong second quarter results, and we expect that our financial performance will continue to track positively with these factors. We believe that Avid has turned an important corner, creating a stronger platform from which to achieve sustainable profitability."

Financial Highlights and Guidance

The company is confirming prior revenue guidance for the full fiscal year 2020 of $64 million – $67 million.

Revenue was $18.3 million for the second quarter of fiscal 2020, an increase of 80% as compared to $10.2 million for the second quarter of last fiscal year. For the six months ended October 31, 2019, revenues were $33.6 million, a 47% increase as compared to revenues of $22.8 million during the prior period. Increases during both current-year periods were primarily due to an increase in the number of in-process and completed manufacturing runs as a result of growing demand from a more diversified client base.

As of October 31, 2019, revenue backlog was approximately $52 million, a decrease of 16% as compared to the first quarter of fiscal 2020. The company expects to recognize the majority of this backlog within the next 12 months.

Gross margin for the second quarter of fiscal 2020 of 18% was up significantly compared to a gross margin of 3% in the prior period. Gross margin for the six months ended October 31, 2019 was 13%, up significantly compared to 7% in the prior period. These increases were primarily attributed to the increased number of manufacturing runs, partially offset by costs associated with the hiring of personnel to accommodate growth in production demand, increases in other compensation expenses, and equipment repairs.

Selling, general and administrative expenses ("SG&A") for the second quarter of fiscal 2020 were $3.5 million compared to $2.8 million for the second quarter of last year. The increase was primarily attributed to payroll and related costs, and stock-based compensation. For the first six months of fiscal 2020, SG&A expenses were $8.0 million compared to $6.0 million for the first six months of fiscal 2019. The increases in SG&A during the six-month period were primarily attributed to payroll and related costs, including one-time employee separation-related expenses, and increased stock-based compensation.

In September 2019, the company recognized a one-time loss of $0.4 million in connection with the termination of a non-manufacturing facility lease, which reduces our future lease and related payments by approximately $1.3 million over the next four years. Additionally, the lease termination released $0.3 million of restricted cash that was pledged as collateral under a letter of credit required by the terminated lease back to the company. The lease termination of this redundant warehouse space has no impact on our future expansion plans, as the company continues to have 42,000 square feet available within our Myford facility.

For the second quarter of fiscal 2020, the company recorded a consolidated net loss attributable to common stockholders of $1.9 million or $0.03 per share, compared to a consolidated net loss attributable to common stockholders of $2.9 million or $0.05 per share, for the prior year period. For the first six months of fiscal 2020, the company recorded a consolidated net loss attributable to common stockholders of $6.1 million or $0.11 per share, compared to a consolidated net loss attributable to common stockholders of $5.9 million or $0.11 per share, for the prior year period.

Avid reported $34.0 million in cash and cash equivalents as of October 31, 2019, compared to $32.4 million on April 30, 2019.
More detailed financial information and analysis may be found in Avid Bioservices’ Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.

Recent Corporate Developments

Launched expanded process development (PD) facility and services. This purpose-built state-of-the-art facility, which houses Avid’s expanded upstream and downstream process development capabilities, represents an important new opportunity for the company by allowing us to expand our existing relationships and attract new business by offering support to customers that seek to outsource their PD work.

Expanded scope of work with multiple existing customers to increase the number of manufacturing batches and/or scale of production.

Appointed Richard (Rich) Richieri as chief operations officer. Mr. Richieri will oversee Process Development, Clinical and Commercial Manufacturing, Technical Support and Facilities. In this role, Mr. Richieri will be focused on streamlining operations, building internal efficiencies and strategic planning for future growth. Mr. Richieri has over 25 years of biopharmaceutical industry experience spanning the areas of drug discovery, CGMP operations, contract manufacturing and process development. Mr. Richieri previously spent 15 years with Avid Bioservices and its former parent company, Peregrine Pharmaceuticals, including the role of senior vice president of manufacturing. During that time, he was instrumental in launching, building and growing Avid’s CDMO business and helping the company diversify its production capabilities.

Initiated final design stage for the construction of a new pharmaceutical grade water system in the Myford facility. Installation of this system will supply water to multiple manufacturing systems, a critical step in creating the manufacturing efficiencies required to increase output and strengthen margins. The company expects the system to be installed in calendar 2020.
Conference Call

Avid will host a conference call and webcast this afternoon, December 9, 2019, at 4:30 PM ET (1:30 PM PT).

To listen to the conference call, please dial (877) 312-5443 or (253) 237-1126 and request the Avid Bioservices conference call. To listen to the live webcast, or access the archived webcast, please visit: View Source

On December 9, 2019 Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan, reported that topline data from the ASCERTAIN phase 3 trial of the orally administered fixed dose combination of cedazuridine and decitabine (ASTX727) in adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML) (Press release, Astex Pharmaceuticals, DEC 9, 2019, View Source [SID1234552105]). The data were featured in an oral presentation given today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting in Orlando, Florida by Dr Guillermo Garcia-Manero, MD, Professor and Chief of Section of Myelodysplastic Syndromes, Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas, on behalf of the study investigators.

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The study was designed as a randomized crossover study comparing oral ASTX727 (100mg cedazuridine and 35mg decitabine fixed dose combination tablet given once daily for 5 days on a 28-day cycle) to IV decitabine (20mg/m2 administered as a daily 1-hour IV infusion for 5 days on a 28 day cycle) in the first 2 cycles with patients continuing to receive oral ASTX727 from Cycle 3 onwards. The data presented demonstrated that the ASCERTAIN study met the primary endpoint of total 5-Day decitabine Area-Under-The-Curve (AUC) equivalence of oral ASTX727 and IV decitabine. The oral/IV decitabine 5-day AUC was 98.9% with a 90% Confidence Interval between 92.7% and 105.6%. Safety findings from the study were consistent with those anticipated with IV decitabine, with no significant differences in the incidence of most common adverse events between ASTX727 and IV decitabine in the first 2 randomized cycles. The most common adverse events (AEs) of any grade >20% regardless of causality in patients in the first 2 randomized cycles who received ASTX727 were thrombocytopenia (43.8%); neutropenia (35.4%); anemia (36.9%); and fatigue (23.8%). Preliminary clinical activity as of the data cutoff was also consistent with published data for IV decitabine. In evaluable patients, the Complete Response (CR) rate was 12%, with an overall response rate, including hematological improvement, of 64%.

"The ASCERTAIN phase 3 study data confirms the hypothesis that by inhibiting cytidine deaminase in the gut, systemic therapeutic concentrations of decitabine can be delivered orally to achieve decitabine systemic exposure equivalent to IV dosing," said Dr Garcia-Manero. "The data support that ASTX727 could become an oral hypomethylating agent alternative to IV decitabine."

"Based on the data from the ASTX727 clinical program, including the ASCERTAIN phase 3 study, Astex is moving ahead with plans to file a New Drug Application (NDA) with the US Food & Drug Administration (FDA)," said Dr Mohammad Azab, MD, President & Chief Medical Officer of Astex Pharmaceuticals, Inc. "Subject to regulatory review and approval, ASTX727 may offer a new option for patients with MDS and CMML that saves them the burden of 5-day IV infusions every month during their treatment period. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to the clinical development program of ASTX727."

ASTX727 is an investigational compound and is not currently approved in any country.

Astex’s parent company, Otsuka Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. previously announced that, subject to regulatory approvals, commercialization of ASTX727 in the US and Canada will be conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. respectively. Astex, Otsuka and Taiho are all members of the Otsuka group of companies.

The presentation can be downloaded from the Astex website at View Source

About Cedazuridine and Decitabine Fixed-Dose Combination (ASTX727)

ASTX727 is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase,1 with the anti-cancer DNA hypomethylating agent, decitabine.2 By inhibiting cytidine deaminase in the gut and the liver, ASTX727 is designed to allow for oral delivery of the approved DNA hypomethylating agent, decitabine, at exposures which emulate exposures achieved with the approved intravenous form of decitabine administered over 5 days.3

ASTX727 has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML (see View Source NCT02103478) and a pivotal phase 3 study (ASCERTAIN) (see View Source NCT03306264) conducted at investigator sites in the US and Canada and designed to confirm the results from the phase 1/2 study. The phase 3 study is now being extended to include patients with acute myeloid leukemia (AML) unsuitable to receive intensive induction chemotherapy.

In September 2019 Astex announced that ASTX727 had received orphan drug designation for the treatment of MDS and CMML from the US FDA.

The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see View Source NCT03502668).

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. US incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.4,5 The prevalence has been estimated to be from 60,000 to 170,000 in the US.6 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.7 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML. CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the US is approximately 1,100 new cases per year,8 and CMML may transform into AML in 15% to 30% of patients.9 The hypomethylating agents decitabine and azacitidine are effective treatment modalities for hematologic cancers and are FDA-approved for the treatment of higher risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.