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Autolus Announces Closing of Public Offering and Full Exercise of Underwriters’ Option to Purchase Additional American Depositary Shares

On April 15, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the closing of its previously announced underwritten public offering in the United States of 4,830,000 American Depositary Shares ("ADSs") representing 4,830,000 ordinary shares, at a public offering price of $24.00 per ADS, which includes an additional 630,000 ADSs issued upon the exercise in full of the underwriters’ option to purchase additional ADSs (Press release, Autolus, APR 15, 2019, View Source [SID1234550820]). Aggregate net proceeds to Autolus, after underwriting discounts but before estimated offering expenses, were $109.0 million. All of the ADSs were offered by Autolus.

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Goldman Sachs & Co. LLC and Jefferies LLC acted as joint book-running managers for the offering. Wells Fargo Securities, LLC and William Blair & Company, L.L.C. acted as lead managers.

The offering was made only by means of a prospectus. The final prospectus related to the offering was filed with the U.S. Securities and Exchange Commission (the "SEC"). Copies of the final prospectus can be obtained from either of the joint book-running managers for the offering, Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at +1 866 471 2526 or by email at [email protected]; or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at + 1 877 821 7388 or by email at [email protected]. For the avoidance of doubt, such prospectus will not constitute a "prospectus" for the purposes of Directive 2003/71/EC (and amendments thereto, including Directive 2010/73/EU, to the extent implemented in each relevant EU member state) and will not have been reviewed by any competent authority in any EU member state.

A registration statement on Form F-1 relating to these securities was declared effective by the SEC on April 10, 2019. The registration statement can be accessed through the SEC’s website at www.sec.gov. This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.

TG Therapeutics Receives Orphan Drug Designation for Umbralisib from the U.S. Food and Drug Administration for the Treatment of Marginal Zone Lymphoma

On April 15, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to its phosphoinositide-3-kinase (PI3K) delta inhibitor, umbralisib (TGR-1202), for the treatment of patients with all three types of marginal zone lymphoma (MZL): nodal, extranodal, and splenic MZL (Press release, TG Therapeutics, APR 15, 2019, View Source [SID1234535144]).

Umbralisib monotherapy is being evaluated in the UNITY-NHL Phase 2b registration directed clinical trial. The MZL cohort of the UNITY-NHL trial is currently evaluating the safety and efficacy of single agent umbralisib in patients with MZL who have received at least one prior anti-CD20 regimen, the same indication for which the FDA recently granted breakthrough therapy designation for umbralisib.

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics, stated "Receiving orphan drug designation for umbralisib in patients with MZL is another important milestone in our commitment to developing novel treatment options for patients with B-cell malignancies, including orphan diseases such as MZL." Mr. Weiss continued, "We are highly encouraged by the interim results presented thus far for the MZL cohort of the UNITY-NHL trial and we look forward to presenting final data from this cohort later this year and to discussing the results with the FDA with the goal of filing for accelerated approval of umbralisib by year-end."

ABOUT ORPHAN DRUG DESIGNATION

Orphan drug designation is granted by the U.S. FDA to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain incentives which may include tax credits towards the cost of clinical trials and prescription drug user fee waivers. If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity.

ABOUT MARGINAL ZONE LYMPHOMA

Marginal zone lymphoma (MZL) comprises a group of indolent (slow growing) B-cell non-Hodgkin lymphomas (NHLs) that begin forming in the marginal zone of lymphoid tissue. With an annual incidence of approximately 7,500 newly diagnosed patients, MZL is the third most common B-cell NHL accounting for approximately eight percent of all NHL cases. MZL consists of three different subtypes: extranodal MZL, nodal marginal zone lymphoma (NMZL), and splenic marginal zone lymphoma (SMZL).

ABOUT THE UNITY-NHL PHASE 2b STUDY—Marginal Zone Lymphoma Cohort

The multicenter, open-label, UNITY-NHL Phase 2b study – Marginal Zone Lymphoma cohort was designed to evaluate the safety and efficacy of single agent umbralisib in patients with MZL who have received at least one prior anti-CD20 regimen. The primary endpoint is overall response rate (ORR) as determined by Independent Review Committee (IRC) assessment. Secondary endpoints include safety, duration of response, and progression-free survival (PFS).

The MZL cohort completed enrollment in August 2018, and in February of 2019 the Company announced that the primary endpoint of ORR as determined by central IRC was met for all treated patients (n=69).

Earlier this month at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, interim data from the UNITY-NHL MZL cohort were presented on the first 42 patients enrolled, demonstrating an ORR of 52%, with a Complete Response (CR) rate of 19%, and a tolerable safety profile amongst all patients treated to date (n=69).

TRILLIUM THERAPEUTICS ANNOUNCES PUBLICATION HIGHLIGHTING ACTIVITY OF TTI-621 IN SÉZARY SYNDROME PATIENTS

On April 15, 2019 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical-stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported the publication of data highlighting the role of TTI-621 in treating patients with Sézary syndrome (SS), a form of cutaneous T-cell lymphoma (CTCL) (Press release, Trillium Therapeutics, APR 15, 2019, View Source [SID1234535141]).

The paper titled "Targeting CD47 in Sézary syndrome with SIRPαFc", published in the April 9th issue of Blood Advances, demonstrates that TTI-621 (SIRPα-IgG1 Fc) triggers macrophage-mediated phagocytosis of Sézary cells and reduces tumor load in SS patients following intravenous administration. Four of five heavily pre-treated SS patients had a decrease in the dominant malignant clone and other markers of tumor burden after a single infusion of TTI-621. "We continue to be excited by the monotherapy data emerging from our TTI-621 clinical studies", stated Dr. Niclas Stiernholm, president and CEO of Trillium Therapeutics. "The results in this manuscript provide further support for investigating the therapeutic potential of our novel CD47-blocking agent in CTCL patients".

CStone received IND approval in China for avapritinib Phase I/II bridging registrational study in patients with advanced gastrointestinal stromal tumors

On April 15, 2019 CStone Pharmaceuticals ("CStone"; HKEX: 2616) reported that the National Medical Products Administration (NMPA) recently approved the initiation of a Phase I/II clinical trial in China evaluating avapritinib, a drug candidate discovered by the company’s partner Blueprint Medicines, in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) (Press release, CStone Pharmaceauticals, APR 15, 2019, View Source [SID1234535138]). This is a stand-alone bridging trial consisting of a Phase I dose-escalation study and Phase II dose-expansion study, with the aim of determining the safety, pharmacokinetics and efficacy of avapritinib in Chinese patients.

GIST, which is classified as a rare disease, is a sarcoma most commonly found in the stomach wall or small intestine, and accounts for about 0.1 to 3.0 percent of all gastrointestinal malignant diseases. GIST is typically diagnosed between the ages of 50 and 80. Approximately 90 percent of GIST cases are linked to mutations that produce over-activation of the KIT or PDGFRA tyrosine kinases, resulting in deregulated cell growth.

Avapritinib has been shown to have broad inhibitory effects on KIT and PDGFRA-driven (primary including D842V mutation) GIST. In January 2019, Blueprint Medicines reported top-line data from the NAVIGATOR Phase 1 clinical trial of avapritinib in patients with advanced GIST, as of a data cutoff date of November 16, 2018.

In 43 patients with PDGFRA Exon 18 mutant GIST treated with a starting dose of 300 or 400 mg once daily (QD), the overall response rate (ORR) was 86 percent (one response pending confirmation). Median duration of response (DOR) was not reached.
In 111 patients with fourth-line or later GIST treated with a starting dose of 300 or 400 mg QD, the ORR was 22 percent (one response pending confirmation). Median DOR was 10.2 months.
Top-line safety results were consistent with those previously reported. Avapritinib was well-tolerated, and most adverse events reported by investigators were Grade 1 or 2. Across all doses (n=237), only 23 patients (9.7 percent) discontinued treatment with avapritinib due to treatment-related adverse events.
In June 2018, CStone and Blueprint Medicines entered into a license and collaboration agreement in which Blueprint Medicines granted exclusive rights to develop and commercialize three drug candidates, including avapritinib, in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

CStone Chairman and CEO Dr. Frank Jiang commented: "Avapritinib has been granted Breakthrough Therapy Designation by the U.S. FDA based on the treatment’s promising data. Currently there are no approved drugs that target the PDGFRA D842V mutation. We hope to leverage the data that will be submitted to the U.S. FDA by Blueprint Medicines and the bridging study results to support an NDA submission in China."

"In February this year, we announced receiving approval for the China arm of the global Phase III VOYAGER clinical trial for avapritinib as a third- or fourth-line therapy in KIT and PDGFRA-driven GIST. We are delighted to receive approval for avapritinib to enter a Phase I/II bridging study, and hope to discover more about this product’s potential in the clinic," said CStone Chief Medical Officer Dr. Jason Yang.

About Avapritinib

Avapritinib is a potent and selective oral inhibitor of KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, and the most potent activity against activation loop mutations, which currently approved therapies for GIST do not inhibit. In contrast with existing multi-kinase inhibitors, avapritinib has shown marked selectivity for KIT and PDGFRA over other kinases. In addition, avapritinib is uniquely designed to selectively bind and inhibit D816V mutant KIT, the primary driver of disease in approximately 95 percent of all systemic mastocytosis (SM) patients. Preclinical studies have shown avapritinib potently inhibited KIT D816V at sub-nanomolar potencies with minimal off-target activity.

Blueprint Medicines is initially developing avapritinib, an investigational medicine, for the treatment of advanced GIST, advanced SM, and indolent and smoldering SM. The U.S. Food and Drug Administration has granted avapritinib two Breakthrough Therapy Designations, one for the treatment of PDGFRA D842V-driven GIST and one for advanced SM.

Tessa Therapeutics Announces Collaboration with Merck Investigating the Combination of KEYTRUDA® (pembrolizumab) and Virus-Specific T Cell Therapy Targeting Human Papillomavirus in Cervical Cancer

On April 15, 2019 Tessa Therapeutics, a clinical-stage immunotherapy company focused on autologous and off-the-shelf, allogeneic therapies targeting solid tumors, reported that it has entered into an agreement with Merck (known as MSD outside the US and Canada), through a subsidiary, to evaluate Tessa’s armored human papillomavirus-specific T cell (HPVST) therapy, or TT12, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with recurrent or metastatic HPV 16 and 18-positive cervical cancer (Press release, Tessa Therapeutics, APR 15, 2019, View Source [SID1234535137]).

Under the agreement, Tessa will conduct a multi-center Phase 1b/2 trial to evaluate the safety and efficacy of the combination. The trial is planned for initiation in the United States, Singapore and South Korea. "We are very excited to work with Merck to evaluate the potential of KEYTRUDA in combination with Tessa’s VST therapy for cervical cancer," said Mr. Andrew Khoo, Tessa Therapeutics CEO and Co-Founder. "Cervical cancer is a major cause of death in women, especially in some of the most vulnerable parts of the world. Furthermore, the current prognosis and treatment options for patients with metastatic cervical cancer are poor. We look forward to developing this novel combination further, which has the potential to bring more effective treatment options for such patients." Tessa’s TT12 is an autologous cell therapy product composed of HPVSTs that have been trained to target HPV 16/18 antigens and genetically modified with a decoy TGF-β receptor to overcome the suppressive tumor microenvironment. The safety and optimal dose selection of armored HPVSTs in combination with another anti-PD-1 antibody is currently being evaluated in a separate, ongoing investigator-sponsored Phase 1 trial in the United States, in patients with relapsed HPV-associated cancers. Preliminary results from this trial show that armored HPVSTs and its combination with anti-PD-1 are well-tolerated, have minimal toxicities and early signs of efficacy. Dr. Ivan D. Horak, M.D., Tessa Therapeutics President of Research and Development said, "Tessa’s TT12 Phase 1 study has shown encouraging results, supporting the effectiveness of armoured HPVSTs in targeting HPV-positive tumors and the addition of anti-PD-1 may remove potential immune inhibition that can hamper the tumor-killing activity of the HPVSTs. Bringing this therapy into a Phase 1b/2 trial and the expansion of clinical sites into Asia reflect our desire to bring novel therapies to more cancer patients globally, as well as our belief in the therapy’s potential to improve the clinical outcomes of patients with advanced stages of HPV-positive tumors." KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA. About Cervical Cancer and Armored HPVST Immunotherapy According to the World Health Organization, cervical cancer is the fourth most common cancer in women worldwide and second most common in less developed regions. Cervical cancer is caused by sexually acquired infection with certain types of human papillomavirus (HPV), with two HPV types (16 and 18) accounting for 70% of cervical cancers and pre-cancerous cervical lesions. Various studies have reported poor outcome of patients with metastatic cervical cancer. Currently, the median survival time for metastatic cervical cancer is only 8 to 13 months[1] and the 5-year survival rate is 16.5% compared to 91.5% for localized cervical cancer[2]. Contrary to patients with early-stage cervical cancer and locally advanced cervical cancer who have access to conventional treatments including surgery, chemotherapy, or radiotherapy, patients with metastatic cervical cancer have no standard treatment because of its heterogeneous manifestations. T cells are a critical part of the body’s immune system that play a central role in fighting virus infections and cancers. Virus-Specific T cells (VSTs), in particular, have the ability to recognize and kill infected cells while activating other parts of immune system for a coordinated response. HPVSTs are produced by collecting patient’s blood and selectively expanding T cells which recognize HPV 16/18 antigens. To increase durability in the tumor microenvironment, the HPVSTs are armored by modifying the cells to express a decoy TGF-β receptor. The armored HPVSTs are expanded before undergoing strict quality control prior to infusion back into the patient.