On January 7, 2019 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for patients with solid tumor cancers, reported that the ongoing multi-center clinical trial of CK-301 has been expanded to enroll patients in three cohorts intended to support requests for accelerated approval and Biologics License Application (BLA) submissions to the U.S. Food and Drug Administration (FDA) (Press release, Checkpoint Therapeutics, JAN 7, 2019, View Source [SID1234532508]). These cohorts include:

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• Microsatellite instability-high (MSI-H) endometrial cancer that has progressed following one or two prior anti-cancer therapies;

• Microsatellite stable (MSS) endometrial cancer that has progressed following one or two prior anti-cancer therapies; and

• MSI-H or mismatch repair deficient (dMMR) colorectal cancer that has progressed on or after, or been intolerant of, previous treatments, including a fluoropyrimidine-and oxaliplatin-and irinotecan-based chemotherapy.

Each cohort is evaluating a fixed dose of 800 mg CK-301 every two weeks (Q2W). The primary endpoint for each cohort is objective response rate (ORR), and secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The ongoing trial is also enrolling cohorts of patients with non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma.

"We are excited to advance our first immuno-oncology drug candidate, CK-301, into these potentially registration-enabling cohorts, representing a significant milestone in the execution of our strategy to obtain multiple accelerated approvals for our anti-PD-L1 antibody," said James F. Oliviero, President and Chief Executive Officer of Checkpoint. "We look forward to presenting interim safety and efficacy data from the ongoing clinical trial in the coming months."

The Phase 1, open-label, multi-center trial is evaluating the safety and tolerability of ascending doses of CK-301 in checkpoint therapy-naïve patients with selected recurrent or metastatic cancers. Following completion of dose escalation in 2018, multiple dose expansion cohorts were initiated. Preliminary data from the ongoing trial suggest that CK-301 is safe and well-tolerated across dose levels ranging from 200 mg to 800 mg administered every two weeks and 1200 mg administered every three weeks, with treatment-related adverse events consistent with marketed anti-PD-1/PD-L1 antibodies.

About CK-301
CK-301 is a fully-human monoclonal antibody of IgG1 subtype that directly binds to Programmed Death Ligand-1 (PD-L1) and blocks the PD-L1 interaction with the Programmed Death Receptor-1 (PD-1) and B7.1 receptors. PD-L1 is an immune-inhibitory checkpoint molecule expressed on epithelial and vascular endothelial cells, as well as by a number of immune cells, and is utilized by tumor cells as an immune escape mechanism. CK-301’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response

On January 7, 2019 Iovance Biotherapeutics, Inc is presented the corporate presentation (Presentation, Iovance Biotherapeutics, JAN 7, 2019, View Source [SID1234532507]).

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On January 7, 2019 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported median overall survival (mOS) in Cohorts 1-4 of the company’s ongoing Phase 1 clinical trial evaluating CLR 131 for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) (Press release, Cellectar Biosciences, JAN 7, 2019, View Source [SID1234532506]). The results showed mOS of 22.0 months among 15 patients, all of whom were heavily pretreated, averaging five prior lines of systemic therapy. Each patient in Cohorts 1-4 of this dose-escalation study received a single 30-minute infusion of CLR 131.

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All patients enrolled in Cohorts 1 through 4 were previously treated with both proteasome inhibitors and immunomodulatory drugs, and experienced disease progression with greater than one-third dual refractory. While no head-to-head studies have been conducted between CLR 131 and other therapies in this heavily pretreated population, for background purposes, a 2016 article published in the journal Bone Marrow Transplantation refractory to both proteasome inhibitors and immunomodulatory drugs achieve mOS of 9 months.1 Additionally, mOS for R/R MM patients receiving treatment in third line averages approximately 12 months of survival, including several recently approved drugs.2,3

"The median overall survival of 22 months in this heavily pretreated patient population is very encouraging. These are patients with limited therapeutic options and, unfortunately, face poor prognoses," said James Caruso, president and chief executive officer of Cellectar Biosciences. "The convenience afforded by CLR 131 delivered in only one or two doses as currently administered in our ongoing hematology studies makes it a far less intrusive regimen than other treatments that must be administered at regular dosing intervals. We believe extending mOS with a more patient-friendly dosing regimen provides both a distinctive product profile and the potential to provide beneficial patient outcomes even in later lines of therapy."

1. R.F Cornell and A.A. Kassim (2016). Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity. Journal of Bone Marrow Transplantation

2. Jurczyszyn et al (2014). New drugs in multiple myeloma – role of carfilzomib and pomalidomide. Contemporary Oncology

3. Dimopolous et al (2016). Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood Review

About the Phase 1 R/R MM Trial

The objective of this multicenter, open-label, Phase 1 dose-escalation study is the characterization of safety and tolerability of CLR 131 administered either as a single-dose or split-dose, 30-minute infusion(s) in patients with R/R MM. In Cohorts 1-4, patients received doses of 12.5 mCi/m2 up to 31.25 mCi/m2. All doses were deemed safe and well tolerated by an independent Data Monitoring Committee (DMC). All 15 patients were heavily pretreated, receiving an average of five previous lines of multidrug therapy including anti-CD38, immunomodulating drugs and proteasome inhibitors. All patients were relapsed or refractory to at least one proteasome inhibitor and IMiD. Most patients presented with advanced stage 2 or 3 disease and 67% had previously received at least one stem cell transplant.

Data from Cohort 5, released in August 2018, evaluated a split or fractionated dose of 31.25 mCi/m2 for tolerability and safety. The dosing schedule provided higher average drug exposure but lower peak serum levels than non-fractionated dosing, potentially reducing adverse events and improving efficacy. The DMC determined the fractionated dose used in Cohort 5 to be safe and well tolerated, and recommended advancement to a higher dose cohort.

In December 2018, Cohort 6 was initiated. Cohort 6 will evaluate up to four patients with each receiving two doses of 18.75 mCi/m2 of CLR 131 administered one week apart. This fractionated dosing regimen will result in each patient being treated with a total of approximately 75.0 mCi of CLR 131, representing an increase in average total exposure of greater than 15% over Cohort 5.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated phospholipid ether-drug conjugate (PDC) therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in R/R MM and a range of B-cell malignancies, and a Phase 1 clinical study in patients with R/R MM exploring fractionated dosing.

The objective of the multicenter, open-label, Phase 1 dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2, as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. Cohort 6 will evaluate up to four patients with each receiving two doses of 18.75 mCi/m2 of CLR 131 administered one week apart. This fractionated dosing regimen will result in each patient being treated with a total of approximately 75.0 mCi of CLR 131, representing an increase in average total exposure of greater than 15% over Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent DMC. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma, as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized PDCs to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

On January 7, 2019 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its unaudited fourth quarter 2018 global net product revenues for ONPATTRO and provided additional updates on the product’s commercial launch (Press release, Alnylam, JAN 7, 2019, View Source [SID1234532505]). These updates will be discussed during a webcast presentation at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco, California today, Monday, January 7, 2019, at 10:30 a.m. PT (1:30 p.m. ET). Specifically, the Company reported:

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ONPATTRO global net product revenues (unaudited) for the fourth quarter of 2018 were $11-12 million.

As of year-end 2018, over 200 patients in the U.S. and EU were receiving commercial ONPATTRO treatment, and approximately 550 total patients worldwide, including patients on commercial drug and patients in clinical studies and in the Company’s global Expanded Access Program (EAP), were being treated with patisiran.

In the U.S., a total of 250 Start Forms were submitted as of year-end 2018. Of these, approximately 50% were from patients previously treated on the ONPATTRO EAP.

The Start Forms came from a diverse range of prescribing physician specialties, including 44% neurologists, 35% cardiologists, and 21% from other specialties.

For Start Forms received, 62% of patients were covered by Medicare, 32% were covered by commercial insurers, and 6% were covered by other government insurers.

Significant progress has been made with value-based agreements (VBAs) in the U.S. and with market access efforts in the EU. Since launch, Alnylam has completed full VBAs with Harvard Pilgrim Healthcare, Humana, and another top five U.S. payer. Additional VBAs are under negotiation with over 15 other commercial payers with the potential to cover over 90% of commercial lives in the U.S.

"2018 was a landmark year for Alnylam, marked by the approval and launch in the U.S. and EU of ONPATTRO, heralding the arrival of RNAi therapeutics as a whole new class of medicines. Our unaudited fourth quarter 2018 global net product revenues of $11-12 million, with over 200 patients receiving treatment with commercial ONPATTRO in the U.S. and EU since launch, reflect strong patient and physician demand and excellent commercial execution by our U.S. and EU teams," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "As we enter 2019, we are excited to continue our global launch of ONPATTRO, bringing the benefits of this innovative therapy to hATTR patients with polyneuropathy around the world, while also working to potentially expand the label for ONPATTRO to include ATTR amyloidosis patients with cardiomyopathy. We also look forward to achieving meaningful milestones across our broad late-stage pipeline of investigational RNAi therapeutics."

In addition, the Company today reported that at December 31, 2018, it had cash, cash equivalents and marketable debt securities, and restricted investments, excluding equity securities, of approximately $1.1 billion (unaudited). The Company intends to provide 2019 financial guidance on non-GAAP R&D and SG&A expenses and year-end cash balance in connection with its full, audited fourth quarter and year-end 2018 financial results in February 2019.

About ONPATTRO (patisiran)

Patisiran, based on Nobel Prize-winning science, is an intravenously administered RNAi therapeutic targeting transthyretin (TTR) for the treatment of hereditary ATTR amyloidosis. It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. Patisiran blocks the production of TTR in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the disease. In August 2018, patisiran received U.S. Food and Drug Administration (FDA) approval for the treatment of the polyneuropathy of hATTR amyloidosis in adults, as well as European Medicines Agency marketing authorization for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy.

Important Safety Information

Infusion-Related Reactions

Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19 percent of ONPATTRO-treated patients experienced IRRs, compared to 9 percent of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, paracetamol, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs,

consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation

ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions

The most common adverse reactions that occurred in patients treated with ONPATTRO were respiratory-tract infection (29 percent) and infusion-related reactions (19 percent).

About LNP Technology

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

On January 7, 2019 Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) reported that the Company will report its financial results for the fourth quarter and full year ended December 31, 2018 before the US financial markets open on February 4, 2019 (Press release, Alexion, JAN 7, 2019, View Source [SID1234532504]). Following the release of the financial results, Alexion management will conduct a conference call and audio webcast at 8:00 a.m. Eastern Time (ET).

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To participate in this conference call, dial 866-762-3111 (USA) or 210-874-7712 (International), conference ID 5972194 shortly before 8:00 a.m. ET. The audio webcast can be accessed on the Investor page of View Source and an archived version will be available for a limited time following the presentation.