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Karyopharm’s Selinexor Receives Fast Track Designation from FDA for the Treatment of Patients with Penta-Refractory Multiple Myeloma

On April 10, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the Company’s lead, oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy (Press release, Karyopharm, APR 10, 2018, View Source [SID1234525246]). The FDA’s statement, consistent with the design of Karyopharm’s Phase 2b STORM study, noted that the three prior lines of therapy include regimens comprised of an alkylating agent, a glucocorticoid, Velcade (bortezomib), Kyprolis (carfilzomib), Revlimid (lenalidomide), Pomalyst (pomalidomide) and Darzalex (daratumumab). In addition, the patient’s disease must be refractory to at least one proteasome inhibitor (Velcade or Kyprolis), one immunomodulatory agent (Revlimid or Pomalyst), glucocorticoids and to Darzalex, as well as to the most recent therapy. The Company expects to report top-line data from the STORM study at the end of April 2018.

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The FDA’s Fast Track program facilitates the development of drugs intended to treat serious conditions and that have the potential to address unmet medical needs. A drug program with Fast Track status is afforded greater access to the FDA for the purpose of expediting the drug’s development, review and potential approval. In addition, the Fast Track program allows for eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, as well as for Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be submitted for review.

"The designation of Fast Track for selinexor represents important recognition by the FDA of the potential of this anti-cancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "We are fully committed to working closely with the FDA as we continue development of this potential new, orally-administered treatment for patients who currently have no other treatment options of proven benefit."

About the Phase 2b STORM Study

In the multi-center, single-arm Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) study, approximately 122 patients with heavily pretreated, penta-refractory myeloma receive 80mg oral selinexor twice weekly in combination with 20mg low-dose dexamethasone, also dosed orally twice weekly. Patients with penta-refractory disease are those who have previously received an alkylating agent, a glucocorticoid, two immunomodulatory drugs (IMiDs) (Revlimid (lenalidomide) and Pomalyst (pomalidomide)), two proteasome inhibitors (PIs) (Velcade (bortezomib) and Kyprolis (carfilzomib)), and the anti-CD38 monoclonal antibody Darzalex (daratumumab), and their disease is refractory to at least one PI, at least one IMiD, Darzalex, glucocorticoids and their most recent anti-myeloma therapy. Overall response rate is the primary endpoint of the study, with duration of response and clinical benefit rate being secondary endpoints. All responses will be adjudicated by an Independent Review Committee (IRC).

About Selinexor

Selinexor (KPT-330) 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. To date, over 2,300 patients have been treated with selinexor, and it is currently being evaluated in several 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), in combination with low-dose dexamethasone (STORM) and as a potential backbone therapy in combination with approved therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more 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.

Halozyme To Host First Quarter 2018 Financial Results Conference Call

On April 10, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that it will webcast its Quarterly Update Conference Call for the first quarter 2018 on Thurs., May 10 at 4:30 p.m. ET/1:30 p.m. PT. Dr. Helen Torley, president and chief executive officer, will lead the call (Press release, Halozyme, APR 10, 2018, View Source [SID1234525245]). On the same date, Halozyme will release financial results for the first quarter ended March 31, 2018 following the close of trading.

The call will be webcast live through the "Investors" section of Halozyme’s corporate website and a recording will be made available following the close of the call. To access the webcast and additional documents related to the call, please visit the Investors page of www.halozyme.com approximately fifteen minutes prior to the call to register, download and install any necessary audio software. The live call may be accessed by dialing (877) 410-5657 (domestic callers) or (334) 323-7224 (international callers) using passcode 769890. A telephone replay will be available after the call by dialing (877) 919-4059 (domestic callers) or (334) 323-0140 (international callers) using replay ID number 68917761.

BeiGene Initiates Global Phase 2 Trial of Anti-PD-1 Antibody Tislelizumab in Patients with Previously Treated Hepatocellular Carcinoma

On April 10, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that the first patient was dosed in a global Phase 2 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, in patients with previously treated advanced hepatocellular carcinoma (HCC or liver cancer) (Press release, BeiGene, APR 10, 2018, View Source;p=RssLanding&cat=news&id=2341754 [SID1234525244]).

"We have made great progress in the development of tislelizumab with three global Phase 3 trials now enrolling patients. Along with our partner, Celgene, we are encouraged by this progress and excited for the development opportunity of tislelizumab globally," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"This potentially registration-enabling trial of tislelizumab is expected to help us further understand its safety and efficacy with respect to the line of treatment in which it is administered to patients with advanced liver cancer. For these patients, as well as for patients in the concurrent front-line Phase 3 study of tislelizumab as compared to sorafenib, we are hopeful that tislelizumab will provide a new treatment option for a patient population with significant unmet needs," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology of BeiGene.

The Phase 2, multi-center trial is designed to evaluate the efficacy and safety of tislelizumab in patients who were previously treated for unresectable HCC. Approximately 225 patients will be enrolled at approximately 75 cancer centers internationally including Greater China (including Taiwan), the United States, and Europe. Patients will receive a 200 mg dose every three weeks.

The trial’s primary endpoint is overall response rate (ORR) evaluated by an Independent Review Committee (IRC), and secondary endpoints include duration of response (DOR), progression-free survival (PFS), disease control rate (DCR) and clinical benefit rate (CBR) assessed by IRC, and overall survival. Additional secondary endpoints include investigator assessed ORR, DOR, PFS, DCR and CBR, safety and tolerability and health-related quality of life.

"I look forward to evaluating tislelizumab for patients with advanced liver cancer, for whom the expected median survival is typically less than one year. Patients who have either not seen benefit from their front-line or even second-line treatments, or who may have lost an initial response, could potentially respond to tislelizumab. We are excited to build upon the knowledge base we have from the dose expansion cohort of patients with HCC from its Phase 1 trial," said Professor Ann-Lii Cheng, M.D., Ph.D., Distinguished Professor and Superintendent of the Cancer Center of National Taiwan University and principal investigator of the trial.

For more information about the trial, patients and physicians should email BeiGene at [email protected].

About Hepatocellular Carcinoma

HCC is a major global health problem, accounting for 85-90 percent of all reported cases of liver cancer.i Liver cancer is the sixth most common type of cancer, with an estimated 782,000 new cases per year worldwide; it was also the second most common cause of cancer-related mortality, responsible for an estimated 746,000 deaths.ii China accounts for approximately 50 percent of both new HCC cases and HCC-related deaths worldwide.ii

About Tislelizumab

Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

TRILLIUM THERAPEUTICS PROVIDES UPDATE ON ITS TTI-621 AND
TTI-622 CLINICAL PROGRAMS

On April 10, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported its TTI-621 and TTI-622 clinical programs (Press release, Trillium Therapeutics, APR 10, 2018, View Source [SID1234525242]). TTI-621 and TTI-622 target CD47, a protein commonly found on the surface of cancer cells. CD47 emits a "do not eat" signal to the immune system, allowing cancer cells to evade detection.

TTI-621 Program

TTI-621 (SIRPa-IgG1 Fc) is a decoy receptor that blocks CD47 and delivers an activating signal to effector cells such as macrophages through its IgG1 Fc region. It is being evaluated in two multi-center clinical trials using intravenous or intratumoral administration and preliminary data from both studies were reported at last year’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Notably, weekly infusions of TTI-621 were shown to be well tolerated and intratumoral injection was observed to reduce local lesions in 9 out of 10 patients with mycosis fungoides, a common type of cutaneous T-cell lymphoma (CTCL). Building upon these monotherapy results, Trillium has refined and focused its TTI-621 clinical program.

"Our thorough signal-seeking efforts in the TTI-621 program have successfully identified T-cell lymphoma as an indication of interest," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. "Consequently, we are now moving forward with a more focused TTI-621 program that reflects our commitment to vigorously pursue this signal in both the intravenous and intratumoral trials."

Recent key modifications to the intravenous dosing study (TTI-621-01, NCT02663518) include:

Focusing near-term efforts on patients with CTCL and peripheral T-cell lymphoma (PTCL). These patients are being enrolled in separate cohorts that will be evaluated using a Simon 2-stage design, with a maximum of 35 subjects in each cohort.
Introducing a standardized intra-subject dose intensification schedule for all newly enrolled subjects to increase drug exposure.
Instituting a number of phase 2-like design elements, such as an independent data monitoring committee and central review of diagnostic pathology as well as radiographic disease imaging.
Recent key changes to the intratumoral dosing study (TTI-621-02, NCT02890368) include:

Increasing the duration of treatment to allow for weekly continuation therapy.
Ability to increase the size of each cohort from 12 to 40 patients based on early signs of clinical benefit.
Establishing new cohorts to study intratumoral TTI-621 in combination with a PD-1 or PD-L1 inhibitor, pegylated interferon-alpha 2a, talimogene laherparepvec (T-vec) or radiation therapy.
TTI-622 Program

TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. TTI-622 consists of the same CD47-binding domain of human SIRPa as TTI-621 but linked to an IgG4 Fc region, which has a more restricted ability to engage activating Fc receptors. It is expected to have a different pharmacologic profile than TTI-621 and is being developed primarily for combination therapy. Like TTI-621, TTI-622 has the advantage of minimal binding to human red blood cells, thereby reducing the risk of anemia and a large antigen sink effect.

"TTI-622 allows us to deepen our presence in the CD47 space," added Dr. Stiernholm. "With this agent we now have two SIRPaFc decoy receptors being evaluated in clinical trials, each with a different level of Fc receptor engagement. We are excited to compare and contrast the activity of these molecules and determine if each has unique applications that could benefit cancer patients."

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation part, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen

Otsuka enters agreement with Takara Bio for co-development and sales rights in Japan to NY-ESO-1 siTCRTM and CD19 CAR gene therapies

On April 9, 2018 Otsuka Pharmaceutical Co., Ltd. reported that it has entered into an agreement with Takara Bio for co-development and exclusive sales rights in Japan for Takara’s NY-ESO-1 siTCRTM (TBI-1301, TBI-1301-A) and CD19 CAR (TBI-1501), both gene therapy products in development for cancer applications (Press release, Takara Holdings, APR 9, 2018, View Source [SID1234591489]).

Under the agreement, the companies will aim for early regulatory approval for the manufacture and sale of the two therapeutic products in Japan. Takara Bio will be responsible for manufacturing and quality control of the two investigational products, while Otsuka will be responsible for clinical trials, other clinical studies, regulatory submissions, product sales and safety data collection. There are no limitations on the target indications in the agreement. Otsuka also holds a right of first refusal for nine Asian countries outside Japan.

Takara Bio will receive upfront and milestone payments from Otsuka, dependent upon the achievement of specified development targets. Takara Bio will supply Otsuka with the products based on specified financial terms. For the NY-ESO-1 siTCRTM gene therapy product, Takara Bio will receive milestone payments upon the achievement of target sales in addition to a running royalty on net sales. The upfront and milestone payments will be up to a maximum total amount of approximately 6.3 billion yen.

Toshiki Sudo, executive director, Research and Otsuka board member noted that, "We are striving to develop innovative products that contribute to the health of humankind around the world, a part of which is co-development cooperation with Takara Bio. We know from our collaboration with Takara Bio on their oncolytic virus HF10 that they have highly advanced biotechnologies and manufacturing facilities dedicated to cell therapy. We aspire jointly to advance biologics research including gene and cell therapy to satisfy currently unsatisfied medical needs."

Masanobu Kimura, Takara Bio board member and president of the Gene Therapy Business Unit, commented that the collaboration with Otsuka, which has broad experience in clinical development, pharmaceutical affairs and sales of pharmaceutical products, will contribute to the development, commercialization and value maximization of the therapeutic products. "We are convinced of further progress on the effective development, aided by the designation of NY-ESO-1・siTCRTM gene therapy product under "SAKIGAKE Designation System" (prioritized review) by the Japanese Ministry of Health, Labour and Welfare on March 27, 2018."

For more information about Takara Bio, please click here: View Source