1stOncology™: Cancer Intelligence Service – Page 11610 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Idera Pharmaceuticals Reports Fourth Quarter and Full Year 2019 Financial Results and Provides Corporate Update

On March 12, 2020 Idera Pharmaceuticals, Inc. ("Idera") (NASDAQ: IDRA) reported on March 11, 2020 its financial and operational results for the fourth quarter and year ended December 31, 2019 (Press release, Idera Pharmaceuticals, MAR 12, 2020, View Source [SID1234555459]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"In 2019, we made great progress with ILLUMINATE-301, our registrational trial of tilsotolimod in combination with ipilimumab in anti-PD-1 refractory patients with advanced melanoma. This was the result of outstanding focus and dedication across our organization and enabled us to finish enrollment in the first quarter of 2020, earlier than anticipated. It also positions us to have initial data from the trial early next year," stated Vincent Milano, Idera’s Chief Executive Officer. "2019 was also notable for our progress in taking tilsotolimod beyond melanoma through both our collaboration in squamous cell carcinoma of the head and neck and through our ILLUMINATE-206 trial, which we initiated in the microsatellite stable colorectal cancer cohort."

ILLUMINATE (tilsotolimod) Clinical Development Update

ILLUMINATE-301: Randomized phase 3 trial of tilsotolimod in combination with ipilimumab versus ipilimumab alone in patients with anti-PD-1 refractory advanced melanoma:

·Primary endpoint family of ORR per RECIST v1.1 and overall survival (OS);
·Trial initiated in March 2018;
·Enrollment completed in March 2020; and
·ORR and other preliminary data expected in Q1 2021.

ILLUMINATE-206: Phase 2, open-label, multicohort, multicenter study to test the safety and effectiveness of tilsotolimod in combination with ipilimumab and nivolumab for the treatment of solid tumors:

·Trial initiated in September 2019 with the microsatellite stable colorectal cancer (MSS-CRC) cohort;

·Initial safety run-in cohort of 10 patients with MSS-CRC fully enrolled; and
·Preliminary data from this cohort expected in Q2 2020.

ILLUMINATE-204: Phase 1/2 trial of tilsotolimod in combination with ipilimumab or pembrolizumab in patients with anti-PD-1 refractory advanced melanoma:

·Enrollment completed in February 2019 at tilsotolimod 8 mg with ipilimumab; and
·Final top-line results from the ILLUMINATE-204 trial, to include ORR, median OS, duration of response (DOR), and safety, are expected to be released in Q2 2020.

Corporate Updates

Since September 30, 2019, the following corporate updates were announced:

·Received new U.S. Patent for tilsotolimod, providing exclusivity through September 2037 when tilsotolimod is used with certain checkpoint inhibitors.
·Entered into private placement financing of up to $97.7 million, with $10.1 million received in December 2019 from initial proceeds and option fees.
·Dr. Jonathan Yingling departed Idera as its Chief Scientific Officer effective January 31, 2020.

Financial Results

Fourth Quarter Results

Revenue in the fourth quarter of 2019 and 2018 was nominal. Research and development expenses for the three months ended December 31, 2019 totaled $8.4 million compared to $8.9 million for the same period in 2018. General and administrative expense for the three months ended December 31, 2019, totaled $3.4 million compared to $3.6 million for the same period in 2018.

Additionally, during the fourth quarter of 2019 the Company recorded $0.6 million and $11.0 million of non-cash warrant revaluation expense and non-cash future tranche right revaluation expense, respectively. These expenses were related to a private placement transaction consummated pursuant to a Securities Purchase Agreement, dated as of December 23, 2019, by and between us and certain institutional investors, whereby the Company sold shares of Series B1 convertible preferred stock and warrants to purchase common stock for $3.9 million and received an upfront option fee of approximately $6.2 million related to certain rights provided to such institutional investors to purchase shares of Series B2, Series B3, and Series B4 convertible preferred stock and warrants to purchase common stock in future tranches, subject to shareholder approval to increase authorized shares. The 2019 period also included non-cash deemed dividends of approximately $28.0 million, increasing net loss attributable to common stockholders, related to the transaction.

As a result of the factors above, net loss applicable to common stockholders for the three months ended December 31, 2019, was $51.3 million, or $1.76 per basic and diluted share, compared to net loss applicable to common stockholders of $12.2 million, or $0.45 per basic and diluted share, for the same period in 2018. Net loss applicable to common stockholders excluding non-cash expense of approximately $11.6 million and deemed dividends of approximately $28.0 million related to the Securities Purchase Agreement for the three months ended December 31, 2019 was $11.7 million, or $0.40 per basic and diluted share.

Full Year Results

Revenue for the year ended December 31, 2019, was $1.5 million compared to revenue of $0.7 million for the same period in 2018. Research and development expenses for the year ended December 31, 2019, totaled $34.9 million compared to $41.8 million for the same period in 2018. General and administrative expenses for the year ended December 31, 2019, totaled $12.5 million compared to $15.4 million for the same period in 2018. Merger-related costs, net for the year ended December 31, 2018, totaled $1.2 million. No such costs were incurred during 2019. Restructuring costs for the year ended December 31, 2019, totaled $0.2 million compared to $3.1 million for the same period in 2018 and related to our decision in July 2018 to wind-down our discovery operations.

The 2019 period also included $0.6 million and $11.0 million of non-cash warrant revaluation expense and non-cash future tranche right revaluation expense, respectively, as well as non-cash deemed dividends of approximately $28.0 million, increasing net loss attributable to common stockholders, as further discussed above under fourth quarter results.

As a result of the factors above, net loss applicable to common stockholders for the year ended December 31, 2019, was $84.6 million or $2.96 per basic and diluted share, compared to net loss applicable to common stockholders of $59.9 million, or $2.25 per basic and diluted share, for the same period in 2018. Net loss applicable to common stockholders excluding non-cash expense of approximately $11.6 million and deemed dividends of approximately $28.0 million related to the Securities Purchase Agreement for the three months ended December 31, 2019 was $45.0 million, or $1.57 per basic and diluted share.

As of December 31, 2019, our cash, cash equivalents, and short-term investments totaled $42.8 million, which includes a $6.2 million contingently refundable option fee received in connection with the December 2019 private placement transaction, discussed above. We currently anticipate that, based on our current operating plan, our current cash, cash equivalents, and short-term investments, excluding the $6.2 million contingently refundable option fee, will fund our operations into the first quarter of 2021.

X4 Pharmaceuticals Provides Corporate Update and Reports Fourth Quarter and Full Year 2019 Financial Results

On March 12, 2020 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases resulting from dysfunction of the CXCR4 pathway, provided a corporate update and reported financial results for the fourth quarter and full year ended December 31, 2019 (Press release, X4 Pharmaceuticals, MAR 12, 2020, View Source [SID1234555458]).

"2019 was a remarkable year for X4, with significant achievements across the entire organization," said Paula Ragan, Ph.D., President and Chief Executive Officer of the Company. "We made important progress advancing our lead therapeutic candidate mavorixafor into pivotal Phase 3 development for patients with WHIM syndrome, while also initiating two proof-of-concept clinical trials in SCN and Waldenström’s, and strengthening both our leadership team and Board of Directors. We’re now well positioned for the years ahead as we focus on near-term clinical trial execution and prepare for key value creation events in our quest to bring new transformative therapies to patients with rare diseases."

Key 2019 Program Achievements and Upcoming Milestones

•Initiated Pivotal Phase 3 Clinical Trial of Mavorixafor for the Treatment of WHIM Syndrome – June 2019: The 4WHIM trial is a pivotal Phase 3 global clinical trial of mavorixafor for the treatment of WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, a rare, inherited, primary immunodeficiency disease.
◦Top-line data from the trial are expected in the second half of 2021.
◦Company to hold Analyst Day, which will also be webcast, on April 7, 2020 to discuss strategic focus on WHIM.
◦Phase 2 open-label extension study data update expected in mid-2020.
•Received Orphan Drug Designation from the European Commission for Mavorixafor for the Treatment of WHIM Syndrome – July 2019
◦Received Scientific Advice from the European Medicines Agency to align the Phase 3 registration trial globally.
•Announced Positive Data from Phase 2a Trial of Mavorixafor in Clear Cell Renal Cell Carcinoma (ccRCC) Patients – September 2019: Data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) demonstrated that mavorixafor, in combination with axitinib yielded clinically meaningful improvements in median progression-free survival (mPFS) in a heavily pretreated advanced ccRCC patient population, and was generally well tolerated.

•Initiated Phase 1b Clinical Trial of Mavorixafor in Patients with Severe Congenital Neutropenia (SCN) – November 2019: The Phase 1b trial is a 14-day, proof-of-concept trial designed to assess the safety and tolerability of daily, oral mavorixafor in up to 45 patients with SCN and other selected congenital neutropenia disorders. The trial will evaluate the neutrophil response and genetic profiles in this patient population as an independent agent or in combination with granulocyte-colony stimulating factor (G-CSF).
◦Initial data from this trial are expected in the second half of 2020.
•Received Breakthrough Therapy Designation from U.S. FDA for Mavorixafor for the Treatment of WHIM Syndrome – November 2019: Highlighting the severity of the disease and the relevance of mavorixafor’s Phase 2 clinical trial data to support the drug’s role as a potential disease-modifying therapeutic option to this underserved patient population, Breakthrough Therapy Designation could expedite the development and regulatory review of mavorixafor.
•Initiated Phase 1b Clinical Trial of Mavorixafor in Combination with Ibrutinib in Patients with Waldenström’s Macroglobulinemia – December 2019: The Phase 1b multi-center, open-label, dose-escalation clinical trial is designed to assess the safety and tolerability of mavorixafor in combination with ibrutinib as well as to obtain certain efficacy signals in patients with Waldenström’s, a rare form of non-Hodgkin’s lymphoma, who have acquired a "gain of function" mutation in CXCR4 in addition to the MYD88 mutation, which is a hallmark of Waldenström’s.
◦Initial data from this trial are expected in the second half of 2020.
•Granted New Composition of Matter Patent by U.S. PTO for Mavorixafor – February 2020: Patent expected to provide exclusivity through 2038.

Key 2019 Corporate Highlights

•Shares of X4 Pharmaceuticals Began Trading on the Nasdaq Capital Market Under the Symbol "XFOR" — March 2019
•Completed Two Public Stock Offerings that Raised Gross Proceeds of $150.8 Million: The first offering was completed in April and the second offering was completed in November.
•Announced Multiple Development and Collaboration Agreements:
◦Announced Collaboration with The Leukemia & Lymphoma Society (LLS) – May 2019: Mavorixafor selected for LLS’ Therapy Acceleration Program (TAP), a strategic initiative creating an alliance to develop mavorixafor for patients with Waldenström’s macroglobulinemia.
◦Announced Partnership with Invitae to Provide No-Cost Genetic Testing to Patients – June 2019: The collaborative PATH4WARD program provides greater access to faster and earlier diagnosis for individuals who may carry genetic mutations known to be associated with WHIM syndrome and SCN.
◦Entered into Oncology Development and Commercialization Agreement with Abbisko for Mavorixafor in Greater China – July 2019: Provided Abbisko Therapeutics with the exclusive rights in China, Taiwan, Hong Kong, and Macau to develop and commercialize mavorixafor in combination with checkpoint inhibitors or other agents in solid tumor oncology indications.
•Strengthened Leadership Team and Board of Directors Throughout the Year: Appointed E. Lynne Kelley, M.D., as Chief Medical Officer and Murray W. Stewart, M.D., to Board of Directors in April 2019; appointed Renato Skerlj, Ph.D., as Senior Vice President of Research and Development and William E. Aliski to Board of Directors in September 2019; appointed Derek Meisner, J.D., as General Counsel in November 2019.

Financial Results

•Cash, Cash Equivalents & Restricted Cash: X4 had $128.1 million in cash, cash equivalents and restricted cash, as of December 31, 2019. We expect that our cash and cash equivalents will fund our operations into early 2022.
•Research and Development Expenses were $7.1 million for the fourth quarter of 2019, and $30.2 million for the year ended December 31, 2019, as compared to $4.7 million and $20.3 million for the comparable periods in 2018, respectively.
•General and Administrative Expenses were $3.9 million for the fourth quarter of 2019, and $17.6 million for the year ended December 31, 2019, as compared to $3.4 million and $8.7 million for the comparable periods in 2018, respectively.
•Net Loss: X4 reported a net loss of $10.8 million for the fourth quarter of 2019, and a net loss of $52.8 million for the year ended December 31, 2019, as compared to a net loss of $11.3 million and a net loss of $33.3 million for the comparable periods in 2018, respectively. Net loss of $52.8 million for the year ended December 31, 2019 includes $3.9 million of non-cash losses related to the sale of in-process research and development intangible assets.

Conference Call and Webcast
The Company will host a webcast and conference call to discuss its fourth quarter and full year 2019 results and provide an update on recent corporate activities today at 8:30 a.m. Eastern Time. The webcast will be accessible under "Events & Presentations" in the Investors page of the Company’s website at www.x4pharma.com. Individuals can participate in the conference call by dialing (866) 721-7655 (domestic) or (409) 216-0009 (international), followed by the conference ID: 3816258.

About Mavorixafor
Mavorixafor is an investigational, oral, targeted therapy that antagonizes the chemokine receptor CXCR4 via allosteric inhibition. The CXCR4 receptor plays a key role in enabling the trafficking of immune cells and effective immunosurveillance. Over-stimulation of CXCR4 results in various immune-system deficiencies. X4 Pharmaceuticals is currently investigating mavorixafor as a once-daily treatment in a global Phase 3 pivotal trial in patients with WHIM syndrome, a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. The FDA has granted Breakthrough Therapy Designation to mavorixafor for the treatment of WHIM syndrome. Mavorixafor is being developed in two proof-of-concept Phase 1b clinical trials – as monotherapy in patients with Severe Congenital Neutropenia (SCN), a group of rare blood disorders characterized by abnormally low levels of white blood cells, and in combination with ibrutinib in patients with Waldenström’s macroglobulinemia, a form of non-Hodgkin’s lymphoma, who have acquired mutations in the CXCR4 receptor.

LEXICON PHARMACEUTICALS REPORTS FOURTH QUARTER AND FULL-YEAR 2019 FINANCIAL RESULTS AND PROVIDES A BUSINESS UPDATE

On March 12, 2020 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), reported financial results for the three months and full-year ended December 31, 2019 and provided a business update (Press release, Lexicon Pharmaceuticals, MAR 12, 2020, View Source;2020.htm [SID1234555457]).

"In 2019, we achieved continued growth in our XERMELO (telotristat ethyl) business of nearly 25% year-over-year and made significant strides in advancing pipeline initiatives such as telotristat ethyl in biliary tract cancer and LX9211 in neuropathic pain," said Lonnel Coats, Lexicon’s president and chief executive officer. "We expect initial clinical efficacy data for telotristat ethyl in biliary tract cancer by the end of this year. As for LX9211, we are initiating a proof-of-concept study in diabetic peripheral neuropathic pain in the first half of this year."

"We received a response yesterday from the Center for Drug Evaluation and Research (CDER) to our appeal of the FDA’s complete response letter (CRL) for sotagliflozin in type 1 diabetes," continued Mr. Coats. "The response confirmed the CRL decision, and we are now evaluating the feedback they provided in their response."

"We are engaged in discussions around potential partnerships for sotagliflozin, which will be necessary to enable completion of the long-term outcomes studies, SCORED and SOLOIST, that are designed to demonstrate benefits in and support labeling for heart failure and chronic kidney disease."

Fourth Quarter and Full-Year 2019 Product and Pipeline Highlights

XERMELO (telotristat ethyl)

•XERMELO U.S. net sales were $31.0 million in 2019.
•In December, Lexicon completed a safety review of the initial safety run-in cohort of The Telotristat Ethyl for Advanced Biliary Tract Cancer, or TELE-ABC, study, a Phase 2a clinical study of telotristat ethyl in patients with biliary tract cancer. Safety analysis from the first six patients who completed at least a 21-day cycle of treatment with telotristat ethyl in combination with cisplatin and gemcitabine supported the continuation of enrollment with no adjustment in the telotristat ethyl 500 mg three times daily dosing regimen.

Zynquista (sotagliflozin)

•In December, Lexicon announced topline data from the Phase 3 SOTA-EMPA study of sotagliflozin in type 2 diabetes. Sotagliflozin 400 mg achieved the primary endpoint of superiority on A1C reduction versus placebo at Week 26 in patients with inadequate glycemic control while on a dipeptidyl peptidase 4 inhibitor, with or without metformin therapy. Sotagliflozin 400mg also achieved the key secondary endpoint of noninferiority versus empagliflozin on A1C reduction from baseline at Week 26. Sotagliflozin was generally well tolerated, with safety results comparable to previously reported safety results in patients with type 2 diabetes.

•In December, Lexicon announced that the U.S. Food and Drug Administration’s (FDA) Office of New Drugs had reiterated the FDA’s prior position that the New Drug Application for sotagliflozin in type 1 diabetes cannot be approved in its present form and denied the appeal of the previously issued CRL. Lexicon subsequently appealed the decision to CDER. As indicated above, CDER yesterday reaffirmed the FDA’s position.

LX9211

•Lexicon announced positive topline Phase 1 data for LX9211 in a multiple ascending dose study in healthy volunteers that demonstrated a favorable safety and pharmacokinetics profile supportive of once-daily dosing.

Fourth Quarter and Full-Year 2019 Financial Highlights

Unless otherwise stated, all comparisons are for the fourth quarter and full year of 2019 compared to the fourth quarter and full year of 2018.

Revenues: Revenues for the fourth quarter decreased to $8.7 million from $17.1 million for the corresponding period in 2018, primarily due to lower revenues recognized under collaboration and license agreements. Full-year 2019 revenues increased to $322.1 million from $63.2 million, primarily due to collaboration revenues recognized from the termination of the alliance with Sanofi and recognition of remaining amounts allocated to the performance obligations from the initial Sanofi collaboration agreement for development activities relating to sotagliflozin, as well as an increase from net product revenue. Net product revenues for full-year 2019 included $31.0 million and $1.3 million, respectively, from net sales of XERMELO in the U.S. and the sale of bulk tablets to Lexicon’s collaborator, Ipsen.

Cost of Sales: Cost of sales related to sales of XERMELO was $0.7 million and $0.6 million, respectively, for the fourth quarter of 2019 and 2018. Full-year 2019 and 2018 cost of sales was $3.2 million and $2.5 million, respectively.

Research and Development (R&D) Expenses: Research and development expenses for the fourth quarter increased to $40.6 million from $12.3 million for the corresponding period in 2018, primarily due to increases in external clinical development costs relating to sotagliflozin subsequent to Lexicon regaining the rights and responsibilities for development and commercialization of sotagliflozin pursuant to the termination of the Sanofi alliance. Full-year R&D expenses for 2019 decreased to $91.9 million from $100.2 million, due to decreases in professional and consulting fees and lower external clinical development costs.

Selling, General and Administrative (SG&A) Expenses: Selling, general and administrative expenses for the fourth quarter were $14.6 million compared to $16.6 million for the same period in 2018. Full-year 2019 SG&A expenses decreased to $56.8 million from $63.8 million, primarily due to lower marketing expenses and professional and consulting costs.

Impairment Loss on Intangible Asset: An impairment loss in 2019 of $28.6 million was recognized to an indefinite lived intangible asset associated with Lexicon’s 2010 acquisition of Symphony Icon, due to the decision to terminate research and development activities related to a program for irritable bowel syndrome that was among the assets acquired.

Income Tax Benefit: An income tax benefit of $6.0 million in 2019 was recognized in connection with the impairment loss on the indefinite lived intangible asset, which resulted in a decrease to the deferred tax liability and created an income tax benefit. During 2018, there was no income tax benefit.

Net Income (Loss): Net loss for the fourth quarter was $51.1 million, or $0.48 per share, as compared to a net loss of $16.8 million, or $0.16 per share, in the corresponding period in 2018. For the fourth quarter 2019, net loss included non-cash, stock-based compensation expense of $3.5 million. For the fourth quarter 2018, net loss included non-cash, stock-based compensation expense of $2.8 million. Net income for the full-year 2019 was $130.1 million, or $1.16 per diluted share, as compared to a net loss of $120.5 million, or $1.14 per share, in 2018. For the full-year 2019, net income included non-cash, stock-based compensation expense of $14.2 million. For the full-year 2018, net loss included non-cash, stock-based compensation expense of $11.7 million.

Cash and Investments: As of December 31, 2019, Lexicon had $271.7 million in cash and investments, as compared to $160.1 million as of December 31, 2018.

Anticipated Near-Term Milestones

•H1 2020 – Initiation of a Phase 2 study for LX9211 in diabetic peripheral neuropathic pain
•H1 2020 – Completion of patient enrollment in the first efficacy cohort of the Phase 2 study of telotristat ethyl in biliary tract cancer
•H1 2020 – Topline results from core Phase 3 sotagliflozin studies in type 2 diabetes
•June 2020 – Presentation of Phase 3 data for sotagliflozin in type 2 diabetes at the 80th Scientific Sessions of the American Diabetes Association (ADA)
•September 2020 – Presentation of Phase 3 data for sotagliflozin in type 2 diabetes at the 56th Annual Meeting of the European Association for the Study of Diabetes (EASD)
•Q4 2020 – Data from the first efficacy cohort of the Phase 2 study of telotristat ethyl in biliary tract cancer

Conference Call and Webcast Information

Lexicon management will hold a live conference call and webcast today at 8:00 am ET / 7:00 am CT to review its financial and operating results and to provide a general business update. The dial-in number for the conference call is 888-645-5785 (U.S./Canada) or 970-300-1531 (international). The conference ID for all callers is 4187725. The live webcast and replay may be accessed by visiting Lexicon’s website at www.lexpharma.com/investors. An archived version of the webcast will be available on the website for 14 days.

About XERMELO (telotristat ethyl)

Discovered using Lexicon’s unique approach to gene science, XERMELO (telotristat ethyl) is the first and only approved oral therapy for carcinoid syndrome diarrhea. XERMELO targets tryptophan hydroxylase, an enzyme that mediates the excess serotonin production within metastatic neuroendocrine tumor (mNET) cells. XERMELO is approved in the United States, the European Union and certain additional countries for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy. Carcinoid syndrome is a rare condition that occurs in patients living with mNETs and is characterized by frequent and debilitating diarrhea. XERMELO targets the overproduction of serotonin inside mNET cells, providing an additional treatment option for patients suffering from carcinoid syndrome diarrhea.

Lexicon has granted Ipsen an exclusive royalty-bearing right and license to commercialize XERMELO outside of the United States and Japan. We are commercializing XERMELO in the United States and Ipsen is commercializing XERMELO in multiple countries, including the United Kingdom and Germany.

XERMELO (telotristat ethyl) Important Safety Information

•Warnings and Precautions: XERMELO may cause constipation, which can be serious. Monitor for signs and symptoms of constipation and/or severe, persistent, or worsening abdominal pain in patients taking XERMELO. Discontinue XERMELO if severe constipation or severe, persistent, or worsening abdominal pain develops.
•Adverse Reactions: The most common adverse reactions (≥5%) include nausea, headache, increased gamma-glutamyl-transferase, depression, flatulence, decreased appetite, peripheral edema, and pyrexia.
•Drug Interactions: If necessary, consider increasing the dose of concomitant CYP3A4 substrates, as XERMELO may decrease their systemic exposure. If combination treatment with XERMELO and short-acting octreotide is needed, administer short-acting octreotide at least 30 minutes after administering XERMELO.

For more information about XERMELO, see Full Prescribing Information at www.xermelo.com.

About Zynquista (sotagliflozin)

Discovered using Lexicon’s unique approach to gene science, Zynquista is an oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney. Zynquista is approved in the European Union (EU) for use as an adjunct to insulin therapy to improve blood sugar (glycemic) control in adults with type 1 diabetes with a body mass index ≥ 27 kg/m2, who could not achieve adequate glycemic control despite optimal insulin therapy. Outside of such approval, Zynquista is investigational and has not been approved by any other regulatory authority for type 1 or type 2 diabetes.

European Commission approves Venclyxto plus Gazyvaro for adults with previously untreated chronic lymphocytic leukaemia

On March 12, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved Venclyxto (venetoclax) in combination with Gazyvaro (obinutuzumab) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (Press release, Hoffmann-La Roche, MAR 12, 2020, View Source [SID1234555456]).

"Venclyxto plus Gazyvaro is the first fixed-duration, chemotherapy-free treatment option that has been shown to help patients with untreated chronic lymphocytic leukaemia live longer without their disease progressing," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "This is an important step forward for adults with this disease in the EU, who will now have an effective treatment option that enables them to end treatment after one year."

The approval is based on results from the primary analysis of the pivotal phase III CLL14 study, which evaluated the combination of 12-month, fixed-duration Venclyxto plus Gazyvaro compared to Gazyvaro plus chlorambucil in adults with previously untreated CLL who had co-existing medical conditions. Results from the primary analysis showed that the combination of Venclyxto plus Gazyvaro led to a 65% reduction in the risk of disease worsening or death (progression-free survival [PFS], as assessed by investigators) compared to Gazyvaro plus chlorambucil, a current standard-of-care for CLL (HR=0.35; 95% CI 0.23-0.53; p<0.0001). When PFS was assessed by an independent review committee, this finding was confirmed. Venclyxto plus Gazyvaro also showed higher response rates (ORR), doubled the complete response rates (CR/CRi) and demonstrated higher rates of minimal residual disease (MRD)-negativity, meaning that no cancer can be detected using a specific and highly sensitive test. In peripheral blood, MRD-negativity rates were 76% for Venclyxto plus Gazyvaro versus 35% for Gazyvaro plus chlorambucil, and in bone marrow MRD-negativity rates were 57% versus 17%, respectively. Results from an updated efficacy analysis (with a median follow-up of 40 months) were consistent with the primary data, and showed that the combination reduced the risk of disease worsening or death by 69% compared to Gazyvaro plus chlorambucil (HR=0.31; 95% CI 0.22-0.44). Safety for Venclyxto plus Gazyvaro appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. The most commonly reported adverse events in people treated with Venclyxto plus Gazyvaro were low white blood cell count (neutropenia), diarrhoea and upper respiratory tract infection.

Results from the CLL14 study further demonstrate Venclyxto’s potential across multiple lines (in the R/R and the frontline settings) in CLL. Previously, the European Commission has approved Venclyxto in combination with MabThera (rituximab) for the treatment of adults with CLL who have received at least one prior therapy, and as a monotherapy for the treatment of CLL in the presence or absence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor. The US Food and Drug Administration (FDA) approved Venclexta in combination with Gazyva for the treatment of people with previously untreated CLL with co-existing medical conditions in May 2019. This followed rapid review and approval of the supplemental New Drug Application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes. Additional submissions of the data to health authorities around the world are still ongoing, with the goal of bringing this new treatment option to more patients as soon as possible.

About the CLL14 study1
CLL14 (NCT02242942) is a randomised phase III study evaluating the combination of fixed-duration Venclyxto plus Gazyvaro compared to Gazyvaro plus chlorambucil in adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclyxto alongside six-month duration of Gazyvaro (Arm A) or six-month duration of Gazyvaro alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyvaro followed by a five-week Venclyxto dose ramp-up to help reduce the risk of tumour lysis syndrome. The primary endpoint of the study is investigator-assessed (INV) progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), minimal residual disease (MRD) status, overall response rate (ORR), complete response rate (CR, with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. MRD-negativity means no cancer can be detected using a specific, highly sensitive test, and was defined as less than one cancer cell in 10,000 leukocytes. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, MD, University of Cologne.

CLL14 study primary analysis results2
Treatment arm Venclyxto + Gazyvaro
(n=216) Gazyvaro + chlorambucil
(n=216)
INV-assessed PFS (primary endpoint)
Median PFS Not reached Not reached
Hazard ratio 0.35 (95% CI 0.23-0.53), p<0.0001
Additional efficacy results (secondary endpoints)
IRC-assessed PFSa
Median PFS Not reached Not reached
Hazard ratio 0.33 (95% CI 0.22-0.51), p<0.0001
Response rates
ORR 85% 71%
CR + complete remission with incomplete bone marrow recovery (CRi) 50% 23%
MRDb
MRD-negative, bone marrow, 57% 17%
p-value p<0.0001
MRD-negative, peripheral blood, 76% 35%
p-value p<0.0001
Safety
Adverse events The most common adverse reactions (≥20%) with Venclyxto plus Gazyvaro were low white blood cell count (neutropenia), diarrhoea and upper respiratory tract infection. The most common serious adverse events in people treated with Venclyxto plus Gazyvaro were febrile neutropenia, pneumonia, infusion-related infection and pyrexia.
a Data at median follow-up of 28 months
b Data at three months following end of combination treatment, in the intention-to-treat population

About Venclyxto (venetoclax)
Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US, under the brand name Venclexta, and commercialised by AbbVie outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the US Food and Drug Administration: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL and two for previously untreated acute myeloid leukaemia.

About Gazyvaro (obinutuzumab)
Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B-cells, but not on stem cells or plasma cells. Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyvaro is marketed as Gazyva in the US.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia, in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 70 countries in combination with chemotherapy for previously untreated follicular lymphoma.

Additional combination studies investigating Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world.3 CLL mainly affects men and the median age at diagnosis is about 70 years.4 Worldwide, the incidence of all leukaemias is estimated to be over 400,000, with an incidence of over 100,000 in Europe.5 CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.3

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies targeting both CD20 and CD3, Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

Sutro Biopharma Announces Extension of First Cytokine Derivative Research Program Under Collaboration with Merck

On March 12, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported that Merck, known as MSD outside the U.S. and Canada, has extended the research term of the collaboration’s first cytokine-derivative program by one year, which includes a payment to Sutro of an undisclosed amount (Press release, Sutro Biopharma, MAR 12, 2020, View Source [SID1234555455]). Sutro’s collaboration with Merck was announced in July 2018 to develop therapeutics for cancer and autoimmune disorders.

"At Sutro, our proprietary and integrated cell-free protein synthesis and site-specific conjugation platform XpressCF+ enables us to design and develop next-generation targeted product candidates by innovating beyond the constraints of cell-based systems," said Sutro CEO, Bill Newell. "The advancement of our novel cytokine-derivative product candidate towards IND-enabling studies marks another important step forward in our collective goal of improving the outcomes for cancer patients."

"In all three of our current collaborations, and in three distinct therapeutic protein formats, we have progressed product candidates either into clinical development or to the late stages of preclinical development," said Sutro Chief Scientific Officer, Trevor Hallam, PhD. "These successes with Merck and with each of our other collaborators demonstrate the power and agility of our rapid and precise engineering platform."