On September 9, 2020 Exscientia, the world-leading, clinical-stage Artificial Intelligence (AI) drug discovery company and Huadong Medicine, the leading Chinese pharmaceutical company, reported that the companies have entered into a co-development partnership to accelerate the discovery of breakthrough small-molecule therapeutics targeted at innovative approach to oncology (Press release, Exscientia, SEP 9, 2020, View Source [SID1234565052]). The first project selected in partnership is focused on transcription control of DNA damage response genes, to treat patients with defective DNA damage repair mechanism, leading to high mutation frequency, as seen is in patients with ovarian cancer and breast cancer.

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Under this collaboration, the pharmatech Exscientia and Huadong will share responsibilities, with Exscientia applying its advanced Centaur Chemist(TM) AI platform to design new molecules against project specific objectives and Huadong Medicine applying its China based experimental and managerial capabilities to generate data and progress Exscientia’s AI design in a rapid closed-loop cycle.

Huadong Medicine Co., Ltd (SZSE 000963), ranked in the top 10 Chinese pharmaceutical companies by Forbes 2020, with more than 10,000 employees and over US $4 Billion annual revenue. The co- development partnership will support both Huadong’s strategy to introduce new medicines in key markets and Exscientia’s aims to advance AI-designed innovative medicines globally.

"This collaboration marks a key step for Huadong on its journey to become an innovation-based pharmaceutical company. We are pleased to work with Exscientia and are fully committed to make this collaboration a success.", said Lyu Liang, Chairman of Huadong.

Professor Andrew Hopkins, CEO of Exscientia, said, "We are very excited to enter the partnership with Huadong Medicine. This innovative partnership provides strategic benefits to Huadong Medicine and Exscientia. We see this as the start of a long-term productive relationship to accelerate novel drug discovery and bring benefits to patients around the globe."

On September 9, 2020 Roche reported that Tecentriq chalked up a surprising failure when used in tandem with chemotherapy paclitaxel in triple negative breast cancer (TNBC) (Press release, Hoffmann-La Roche, SEP 9, 2020, View Source [SID1234565000]). The FDA has taken notice, issuing a warning that might spell trouble for a conditional nod of the PD-L1 agent.

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On Tuesday, the FDA alerted the public that the Tecentriq-paclitaxel combo didn’t work in a clinical trial in previously untreated locally advanced or metastatic TNBC and warned doctors not to use it.

The thing is, Tecentriq already holds a similar approval in TNBC, which it won in March 2019—and it’s that nod that could be in jeopardy. "Continued approval … may be contingent on proven benefit of the treatment in additional trials," the FDA said.

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Tecentriq’s green light, restricted to PD-L1-expressing cases, is for a combination with Celgene’s Abraxane, or paclitaxel protein-bound, a formulation where paclitaxel is bound to albumin nanoparticles in a delivery mechanism that helps the drug concentrate in areas of tumor.

That conditional approval was based on data from the phase 3 IMpassion130 study, which showed that Tecentriq-Abraxane cut the risk of disease worsening or death by 40% over Abraxane alone in PD-L1-positive, previously untreated TNBC patients.

RELATED: Roche swings and misses with another Tecentriq-chemo combo in tough-to-treat breast cancer

However, in the phase 3 IMpassion131 trial, adding Tecentriq to paclitaxel didn’t stall tumor progression in newly diagnosed PD-L1-positive patients. To make it worse, interim results even favored solo paclitaxel in terms of life extension, though Roche said the data were not conclusive.

Based on the latest trial failure, the agency said it would review the findings and announce any changes to Tecentriq’s prescribing information.

In a statement, a spokesperson at Roche’s Genentech declined to comment on whether the IMpassion131 failure might affect Tecentriq’s approved TNBC use, only saying the company is in active discussions with the FDA.

Of course, IMpassion131 might not threaten the existing indication after all. First, compared with conventional paclitaxel, Abraxane is linked to preferential uptake into cancer cells and, hence, potentially offers a better anti-tumor effect thanks to its unique delivery tech.

Plus, I-O drugs have put up failures in confirmatory trials before, but so far none have led to the FDA terminating an approval. Tecentriq itself in 2017 flopped a phase 3 trial in previously untreated bladder cancer, but it still got to keep a go-ahead based on phase 2 tumor response data. In June, Merck & Co.’s rival PD-1 drug Keytruda, whether on its own or used in combination with chemotherapy, also failed to significantly keep bladder tumors at bay compared with chemo. But that drug may not lose its conditional approval, either; there’s no word yet from the FDA.

On September 9, 2020 The National Institute for Heath and Care Excellence (NICE) reported that it has turned down NHS funding of Revlimid (lenalidomide) as maintenance treatment after an autologous stem cell transplant for newly diagnosed multiple myeloma in adults (Press release, Celgene, SEP 9, 2020, View Source [SID1234564993]).

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There is currently no maintenance treatment for newly diagnosed multiple myeloma in people who have had an autologous stem cell transplant; the condition is usually monitored until it gets worse.

Clinical trial results show that, compared with monitoring alone, Revlimid increases how long people live and also extends the time before the condition gets worse.

However, NICE has concluded in preliminary guidelines that cost-effectiveness estimates for the drug in this setting "are uncertain".

"This is because of limitations in the cost-effectiveness model, and because the model might not reflect what happens in the NHS in England," it said.

Therefore, Revlimid could not be considered value for money for the NHS when used for this indication, it noted.

On September 9, 2020 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 that a clinically meaningful 40% overall response rate (ORR) was observed in the subset of refractory multiple myeloma patients deemed triple class refractory who received a total administered dose of 60 mCi or greater (Press release, Cellectar Biosciences, SEP 9, 2020, View Source [SID1234564949]). Triple class refractory is defined as patients refractory to immunomodulatory, proteasome inhibitors and anti-CD38 antibody drug classes.

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The 40% ORR (6/15 patients) represents triple class refractory patients enrolled in Part A of Cellectar’s CLOVER-1 study and additional patients enrolled in Part B from March through May 2020. As a reminder, all patients being enrolled in Part B are required to be triple class refractory. The additional six patients were heavily pre-treated with an average of 9 prior multi-drug regimens. Three patients received a total administered dose of greater than 60 mCi and three received less than 60 mCi. Consistent with the data released in February 2020, patients receiving greater than 60 mCi exhibit strong responses. Patients continue to tolerate CLR 131 well, with the most common and almost exclusive treatment emergent adverse events being cytopenias and importantly, no unexpected adverse events have been reported.

"We remain encouraged by the consistency of CLR 131’s efficacy and tolerability data in these extremely challenging to treat triple class refractory multiple myeloma patients," said Dr. John Friend, CMO of Cellectar Biosciences. "A 40% ORR is a clinically meaningful outcome. For reference purposes, two recently approved drugs received a 25% and 31% ORR in triple class refractory patients. We look forward to the further development of CLR 131, a first in class phospholipid radio conjugate that may provide a significant benefit to patients and treatment alternative for clinicians."

About CLOVER-1

The Phase 2 CLOVER-1 study is an open-label study designed to determine the efficacy and safety of CLR 131 in select B-cell malignancies. The CLOVER-1 Phase 2 study completed the Part A dose-exploration portion, conducted in relapsed/refractory (r/r) B-cell malignancies, and is now enrolling in the Part B expansion cohorts evaluating ≥ 60 mCi total body dose and 2 cycle doses as patients have demonstrated a clinically meaningful response and predictable safety profile of CLR 131 in r/r multiple myeloma (MM) and lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia (LPL/WM). Patients with LPL/WM must have received at least two prior treatment regimens, unless ineligible to receive standard agents, and have measurable disease, as defined by either a nodal lesion of >15 mm, an extranodal lesion of >10 mm, or measurable IgM. Prior external beam radiation therapy was allowed. The median age of the four LPL/WM patients enrolled in the study was 70 (range 54-81) and included 2 females and 2 males who had a median of two prior regimens (range 1-5). CLR 131 was administered intravenously, up to 30 minutes.

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

About CLR 131

CLR 131 is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells unlike many traditional on-market treatment options. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-cell lymphomas, and a Phase 1 dose-escalating clinical study in pediatric solid tumors and lymphomas. The company recently completed a Phase 1 dose-escalation clinical study in r/r multiple myeloma. The FDA granted CLR 131 Fast Track Designation for both r/r multiple myeloma and r/r diffuse large B-cell lymphoma and Orphan Drug Designation (ODD) for the treatment of multiple myeloma, lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia, neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. CLR 131 was also granted Rare Pediatric Disease Designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. Earlier this year, the European Commission granted an ODD for r/r multiple myeloma and most recently, the U.S. Food and Drug Administration granted Fast Track Designation for CLR 131 in lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM) in patients having received two prior treatment regimens or more.

On September 9, 2020 PDL BioPharma, Inc. ("PDL" or the "Company") (Nasdaq: PDLI) reported the closing of the sale of its wholly owned subsidiaries Noden Pharma DAC and Noden Pharma USA (collectively "Noden") to Stanley Capital (Press release, PDL BioPharma, SEP 9, 2020, View Source [SID1234564915]). The total value of the transaction will result in payments to PDL of up to $52.83 million in cash, $4.58 million greater than previously announced .

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"After running an extensive process, we are excited about closing this transaction with Stanley Capital," commented PDL’s President and CEO Dominique Monnet. "It represents the completion of a key divestiture for PDL and an exciting opportunity for the Noden team."

Payments to PDL, in connection with the closing of the transaction, are $12.72 million. The agreement provides for an additional $33 million to be paid to PDL in 12 equal quarterly installments from January 2021 to October 2023 and two potential contingent payments totaling $3.25 million. There is an additional $3.86 million to be paid to PDL in four equal quarterly installments from January 2023 to October 2023, primarily due to the incremental cash accumulated in the business since July 31, 2020.

Together with their advisors, Torreya and SVB Leerink, PDL’s board of directors and management team evaluated a number of potential transactions to maximize stockholder value for Noden. Torreya was retained by PDL to explore potential strategic transactions and assist in the disposition of Noden, while SVB Leerink has been engaged by PDL to advise on overall liquidation and distribution strategies.

In addition to the cash proceeds from the sale to Stanley Capital, PDL believes that this transaction may qualify for some Federal tax benefit under the CARES Act. In connection with its monetization process, PDL expects to execute transactions in 2020 that may result in the recognition of ordinary tax losses that, under the CARES Act, could be applied to prior tax years in which PDL was a substantial tax payor. At this time, however, there can be no assurance that such tax benefits will be realized.