On June 19, 2019 Gilead Sciences, Inc. (Nasdaq: GILD) and Nurix Therapeutics, Inc., a company discovering drugs that harness the body’s natural process to control protein levels, reported a global strategic collaboration to discover, develop and commercialize a pipeline of innovative targeted protein degradation drugs for patients with cancer and other challenging diseases (Press release, Gilead Sciences, JUN 19, 2019, View Source [SID1234537166]).

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This press release features multimedia. View the full release here: View Source

Dysregulated and/or mutated proteins play a central role in the development and progression of many human diseases. Nurix’s technology platform is focused on the manipulation of the ubiquitin system and its component E3 ligases, the key enzymes responsible for controlling protein levels in human cells.

Under the multi-year collaboration, Nurix will utilize its proprietary drug discovery platform to identify novel agents that utilize E3 ligases to induce degradation of specified drug targets and Gilead will have an option to license drug candidates directed to up to five targets resulting from the work. Nurix will retain the option to co-develop and co-detail up to two programs in the United States. The collaboration excludes Nurix’s lead degradation program, for which Nurix retains all rights.

"There are many molecular targets involved in disease pathways that have traditionally been challenging to manipulate using conventional approaches," said John McHutchison, A.O., M.D., Chief Scientific Officer and Head of Research and Development, Gilead Sciences. "Nurix’s innovative protein degradation discovery technology provides Gilead with a new strategy to interrogate these drug targets, as we continue to build a pipeline of small molecule therapeutics for patients with cancers and other diseases."

"Gilead is an ideal partner to help us bring potentially transformative treatments to patients," said Arthur T. Sands, M.D., Ph.D., Nurix’s Chief Executive Officer. "This partnership expands our ability to build our pipeline of novel targeted protein degradation drugs based on our established expertise in the field of protein homeostasis, while we continue to independently advance our lead programs into the clinic."

Under the terms of the agreement, Nurix will receive an upfront payment of $45 million and will be eligible to receive up to approximately $2.3 billion in total additional payments based on the successful completion of certain research, pre-clinical, clinical, regulatory and commercialization milestones as well as up to low double-digit tiered royalties on net sales. For those programs that Nurix opts in to co-develop and co-detail, the parties will split development costs as well as profits and losses 50/50 for the U.S., and Nurix will be eligible to receive royalties on ex-U.S. sales and reduced milestone payments.

On June 19, 2019 Pacira BioSciences, Inc. (Nasdaq: PCRX) reported the appointment of Max Reinhardt as the company’s president (Press release, Pacira Pharmaceuticals, JUN 19, 2019, View Source [SID1234537164]). Mr. Reinhardt will report to Dave Stack, chairman and chief executive officer of Pacira, and be responsible for overseeing all commercial and medical affairs functions at Pacira. Mr. Stack will maintain leadership of the Pacira commercial and corporate strategy.

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Mr. Reinhardt was most recently Vice President of Marketing for DePuy Synthes, part of the Johnson & Johnson Medical Devices Companies, where he was accountable for $5.5 billion in revenue from its comprehensive portfolio of solutions for medical specialties including joint reconstruction, trauma, craniomaxillofacial, spinal surgery and sports medicine. Mr. Reinhardt also led the DePuy Synthes alliance strategy, which included managing its partnership with Pacira.

"We are delighted to officially welcome Max to the Pacira team. Having worked closely with him throughout our partnership with Johnson & Johnson, I am confident that Max’s vast experience successfully commercializing products across a variety of surgical specialties will be of great benefit to Pacira as we continue to drive robust EXPAREL growth and integrate the ioveraº system into our commercial offering," said Dave Stack, chairman and chief executive officer of Pacira. "Max’s commitment to reducing or eliminating opioid exposure directly aligns with our corporate mission and we are excited to add his expertise to our leadership team as we work towards becoming a premier provider of innovative non-opioid pain management and regenerative health solutions."

"Working with Pacira over the last two years, I have seen firsthand the accelerating role of EXPAREL as the foundation of opioid-sparing pain management protocols," said Mr. Reinhardt. "Looking ahead, I believe there is tremendous potential for EXPAREL-based enhanced recovery pathways to optimize patient outcomes in both orthopedic and soft tissue surgeries, particularly when considering the ways in which anesthesiologists are driving change by implementing EXPAREL-based regional approaches as the core of non-opioid multimodal strategies. With iovera° we have the unique opportunity to solidify our leadership in non-opioid pain management by offering healthcare providers a total procedural solution for low- or no-opioid total knee arthroplasty procedures. I am looking forward to working with this talented team and expect this transition will be seamless."

Mr. Reinhardt has more than 20 years of medical device experience highlighted by increasing sales and marketing leadership roles. Prior to serving as Vice President of Marketing at DePuy Synthes, Mr. Reinhardt was Director of Sales and Marketing for DePuy Spine and Vice President of US Sales for DePuy Spine. In 2011, he was named Vice President, Worldwide Marketing, a position in which he played a key role in the acquisition and integration of Synthes Spine. In 2012, he was named Worldwide President, DePuy Synthes Spine, and led the spine business through the first two years of integration. Prior to Johnson & Johnson, Mr. Reinhardt served in sales leadership roles at both Olympus KeyMed and STERIS Corporation in the UK.

Mr. Reinhardt earned his Higher National Diploma at Sparsholt College of Agriculture in the U.K. and his Master of Science degree in marketing from the University of Hull, England

On June 19, 2019 Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento") reported that its Chairman and CEO, Dr. Henry Ji will be discussing the progress made, including innovative higher potency Dimeric Antigen Receptor ("DAR") technology and allogeneic knock-out/knock-in ("KOKI") cell therapy manufacturing advances related to its CD38 immunotherapies at upcoming industry conferences, investor conferences and investor meetings (Press release, Sorrento Therapeutics, JUN 19, 2019, View Source [SID1234537163]). The reference presentation in support of those update discussions has been uploaded to the Sorrento investor relations website and was filed today with the Securities and Exchange Commission ("SEC") on a Current Report on Form 8-K.

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Key progress update areas that will be discussed include:

Clinical Proof-of-concept Study for Anti-CD38 Autologous CAR-T Cell Therapy

The Sorrento suite of anti-CD38 immunotherapies is based on a fully human anti-CD38 antibody mined from the Sorrento G-MAB antibody library. This antibody has demonstrated unique functional binding properties, which make it a promising candidate for therapeutic applications.

Dr. Evren Alici’s research team at the Karolinska Institutet and Hospital in Stockholm, Sweden, has generated preclinical data demonstrating that this anti-CD38 antibody can be effectively used in chimeric antigen receptors ("CAR-T") and antibody-drug conjugates ("ADC") retaining its anti-tumor activity against multiple myeloma cells obtained from patients who had previously failed anti-CD38 therapy with daratumumab (Darzalex).

The current anti-CD38 CAR construct has also enabled successful manufacturing of autologous CAR-T cells using retrovirus-based cGMP manufacturing processes. The CAR-T cells obtained in this traditional approach have been successfully administered to multiple myeloma patients. Patient recruitment is currently ongoing at two clinical sites and additional sites will be opened in the second half of 2019.

"Our CD38 CAR-T program remains an active clinical stage trial with relapsed or refractory multiple myeloma ("RRMM") patients being dosed and recruitment proceeding as expected. We are particularly proud of our production site at Sorrento in San Diego producing the clinical CD38-CAR-T cells used in our study," stated Dr. Jerome Zeldis, Chief Medical Officer of Sorrento. "Given the high level of interest in our program, we look forward to publicly discussing our study data later this year."

Next-Generation Anti-CD38 Non-viral KOKI Allogeneic DAR-T Cell Therapy

The key components/steps of current state-of-the-art CAR-T cell therapy programs are: a) CAR architecture; b) viral-based transduction of the CAR construct into the T cells; and c) using the patients as their own source for these autologous T cells. Sorrento has developed disruptive next-gen technology platforms to address each of these components/steps. The research and development team at Sorrento has pioneered an allogeneic ("off-the-shelf") cell therapy technology (KOKI DAR-T) that utilizes healthy donor T cells and genetically ("non-virally") modifies them with a novel DAR construct (see the public presentation accompanying this press release).

Our proprietary design of the dimeric antigen receptor ("DAR") is based on utilizing the complete antigen-binding fragment (Fab) of the parental antibody. It is generally accepted that Fabs more closely mimic the functional and biophysical properties of natural antibodies. Utilizing the same antibody binding domain sequence, we have compared CAR constructs to their corresponding DAR constructs. Our data showed that the DAR-T cells exhibited a higher cytotoxicity against target-expressing tumor cells as compared to CAR-T cells. In preclinical mouse models, the DAR-T cells demonstrated increased anti-tumor potency as well.

Our non-viral KOKI technology may offer several potential benefits over existing virus-based technology, such as transgene-encoding lentiviruses or retrovirus, to introduce antigen receptor constructs into pre-screened healthy donor (allogeneic) T cells. These potential advantages of our non-viral KOKI technology include: a) site-specific integration of transgenes into a pre-selected locus in the T cell genome; b) enhanced clonal expansion of the DAR-T cells; and c) streamlined method for transgene construct production without need for laborious and time-consuming virus production, release and validation processes, resulting in a shorter research and development timelines for IND-enabling activities.

Another major drawback of current CAR-T therapy is the reliance on patients’ own T cells (autologous therapy). This leads to delays in treatment (vein-to-vein time of several weeks) and substantial manufacturing costs due to the individual processing of each patient sample. By utilizing healthy donor T cells as the starting point in our KOKI DAR-T cell technology these concerns can be effectively addressed.

Sorrento has developed a robust manufacturing process in which these donor-derived KOKI DAR-T cells are expanded and purified resulting in the production of hundreds of KOKI allogeneic DAR-T cell doses per manufacturing run from a single healthy donor in about 2 weeks. This has the potential to substantially reduce cost of goods sold ("COGS") and expand access to cell therapy to patients. This KOKI DAR-T manufacturing process will enable Sorrento with its current manufacturing staff to produce in its existing San Diego cGMP facilities the non-viral CD38 DAR-T cells for "off-the-shelf" treatments for thousands of cancer patients per year. Notably, allogeneic cell therapies will enable the execution of global trials and potential commercialization as the shipping logistics and distribution will be simplified. In addition, certain countries’ restrictions on patient cell shipping and processing currently hampering CAR-T cell therapy studies will not prevent patients from receiving KOKI DAR-T cell treatments.

"Our first clinical program will be KOKI allogeneic CD38 DAR-T cell therapy. Preclinical data and clinical trial designs will be shared and discussed with the clinical and scientific community as well as investors once the IND has been accepted and the clinical study initiated", said Dr. Henry Ji, Chairman and CEO of Sorrento. "We are currently applying our KOKI allogeneic DAR technology to our cell therapy program pipeline for multiple hematological and solid tumor indications, including: multiple myeloma, lymphoma, liver cancer, sarcoma, pancreatic cancer and glioma."

Anti-CD38 Antibody-Drug Conjugate STI-6129

In keeping with off-the-shelf immunotherapy strategy, Sorrento is developing STI-6129 (or LNDS1001 for China), an anti-CD38 ADC, for which we plan the IND submission in the second half of 2019. Preclinical studies have demonstrated strong anti-tumor activity. Notably, the toxin payload of the ADC is based on our proprietary tubulin inhibitor Duostatin5. The required toxicology studies of the ADC showed a promising safety profile. The manufacturing of the GMP drug substance of the ADC was successfully completed at our facility in Suzhou, China. The clinical drug product will be manufactured at Bioserv, our wholly-owned San Diego-based fill/finish service provider. We anticipate initiation of clinical studies in hematological malignancies and potentially non-oncology indications by the end of 2019.

"In total, all of our anti-CD38 immunotherapies have been discovered, developed and manufactured in-house by our outstanding R&D and manufacturing team members. This demonstrates the unique and efficient "turn-key" approach as we are able to perform with our immunotherapy R&D teams utilizing internal expertise and capabilities without being dependent on external service providers," said Dr. Henry Ji, Chairman and CEO of Sorrento. "We believe that this anti-CD38 therapy suite illustrates the depth and breadth of the disruptive technology platforms we have to attack diseases with high unmet medical need from different angles. Each modality has its unique strengths but when properly sequenced in the clinic by our outstanding clinical development team, we believe substantial benefit potential can be provided to patients, their caretakers and the medical community. We see our CD38 Therapeutics business unit as a model for our vision and will apply this approach to a variety of therapeutic targets, including CD19, BCMA, and CEA."

On June 19, 2019 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported updated results from the Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study evaluating selinexor, the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue and CAR-T (chimeric antigen receptor modified T cell) therapy (Press release, Karyopharm, JUN 19, 2019, View Source [SID1234537162]). The data were highlighted in an oral presentation at the 2019 International Conference on Malignant Lymphoma (ICML) being held June 18-22, 2019, in Lugano, Switzerland.

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Top-line results for the SADAL study were previously presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting in December 2018. The results being presented at ICML remain consistent with those reported at ASH (Free ASH Whitepaper) and include efficacy results from the final 12 patients who had not reached their first response assessment in time to be included in the previously released top-line efficacy analyses. For the SADAL study’s primary endpoint, single-agent selinexor achieved an overall response rate (ORR) of 28.3%. Two additional patients achieved a complete response (CR) since the ASH (Free ASH Whitepaper) presentation for a total of 13 CRs and a CR rate of 10.2% in these patients with heavily pretreated relapsed or refractory DLBCL. Key secondary endpoints included a median duration of response (DOR) in the responding patients of 9.2 months and median overall survival (OS) across the entire study population of 9.0 months.

"Single-agent oral selinexor continues to demonstrate encouraging response rates in these heavily pretreated patients with DLBCL who have received two or more prior therapies and are not eligible for transplantation or CAR-T therapy, and have limited therapies available to treat their disease," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We look forward to sharing these data with the U.S. and European regulatory authorities and plan to seek regulatory approval of selinexor as a potential new therapeutic option for patients battling highly refractory DLBCL."

Karyopharm expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the first half of 2020. These submissions will include requests for accelerated approval and conditional approval, respectively, of selinexor as a treatment for patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for stem cell transplantation, including CAR-T therapies. In addition to Orphan Drug Designation, selinexor was granted Fast Track designation by the FDA in 2018 for the patient population evaluated in the SADAL study.

Updated Phase 2b SADAL Results

Among the 127 patients (median of 2 prior treatment regimens with a range 1-6) who were evaluable for response, as adjudicated by an independent central radiological committee, 36 patients responded (13 CRs and 23 partial responses (PRs)) for an ORR of 28.3%. An additional 11 patients experienced stable disease (SD) for a disease control rate of 37.0%. Selinexor also demonstrated deep and durable responses in patients with either GCB or non-GCB subtypes of DLBCL: the ORR in the 59 patients with the GCB-subtype was 33.9% and the ORR was 20.6% in the 63 patients with the non-GCB subtype. In addition, there were 5 patients enrolled whose subtype was unclassified and 1 of these patients achieved a CR while 2 of these patients achieved a PR.

The median DOR across responding patients was 9.2 months and responses tended to occur rapidly. Median OS for the entire patient population was 9.0 months while median OS has not yet been reached in patients who achieved either a CR or PR. Patients whose disease progressed or had no response to selinexor had a median OS of 4.1 months, which is consistent with the expected poor prognosis for patients who have relapsed or refractory DLBCL and have been previously treated with 2 or more lines of therapy.

All 127 patients were included in the safety analyses. The most common treatment-related adverse events (AEs) were cytopenias along with gastrointestinal and constitutional symptoms and were generally reversible and managed with dose modifications and/or standard supportive care. The most common non-hematologic AEs were nausea (52.8%), fatigue (37.8%), and anorexia (34.6%) and were mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 AEs were thrombocytopenia (39.4%), neutropenia (20.5%) and anemia (13.4%) and were generally not associated with clinical sequelae.

Details for the ICML 2019 oral presentation are as follows:

Title: A Phase 2b Study of Selinexor in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): SADAL Trial
Lead author:Nagesh Kalakonda, University of Liverpool
Abstract #: 031
Session: Focus On: Results from Single-Agent Trials
Date and Time:Wednesday, June 19, 2019; 17:25 – 17:45 CEST
Location: Auditorium (USI Università)

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) seeking accelerated approval has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients based on data from the STORM study. The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval. Selinexor is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On June 19, 2019 Abbott (NYSE: ABT) reported that it will announce its second-quarter 2019 financial results on Wednesday, July 17, 2019, before the market opens (Press release, Abbott, JUN 19, 2019, View Source [SID1234537161]).

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The announcement will be followed by a live webcast of the earnings conference call at 8 a.m. Central time (9 a.m. Eastern), and will be accessible through Abbott’s Investor Relations website at www.abbottinvestor.com. An archived edition of the call will be available later that day.