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Siamab Therapeutics Announces Publication of New Data on its ST1 Lead Program in the Journal Oncotarget

On May 1, 2018 -Siamab Therapeutics, Inc., a biopharmaceutical company developing novel glycan-targeted cancer therapeutics, reported the publication of new preclinical data for its ST1 antibody drug conjugate (ADC) targeting the tumor-associated carbohydrate antigen (TACA) Sialyl-Tn (STn) (Press release, Siamab Therapeutics, MAY 1, 2018, View Source [SID1234525900]). STn is present on multiple solid tumors and is associated with a chemoresistant population in ovarian cancer. The findings show that ST1-ADC selectively inhibits tumor cell proliferation and induces tumor cell death in both in vitro and in vivo ovarian cancer models. ST1, Siamab’s lead program, is in late stage preclinical development for the treatment of STn-expressing solid tumors. The data, generated through a collaboration with Bo Rueda, Ph.D., Director of The Vincent Center for Reproductive Biology at Massachusetts General Hospital, have been published online in the journal Oncotarget.

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The published study results show that STn is expressed on ovarian cancer cells and is frequently co-expressed with the established ovarian cancer stem cell (CSC) marker CD133. Importantly, STn positive and CD133 positive cells persist following cytotoxic chemotherapy. Furthermore, the results show that treatment with Siamab’s ST1 ADCs reduced the viability of STn positive ovarian cancer cell lines in vitro and reduced tumor volume in vivo in an ovarian cancer xenograft mouse model, depleting STn positive tumor cells. No significant changes in mouse weight were observed during treatment and no other toxicities were noted.

"These findings are important as they hold promise for the development of new therapeutic options to treat ovarian cancer," said Jeff Behrens, president and chief executive officer of Siamab. "The results show that targeting the STn antigen expressed on ovarian tumor cells and, critically, chemoresistant cells, with an anti-STn ADC can selectively inhibit tumor cell proliferation and induce tumor cell death in both in vitro and in vivo models. Furthermore, the studies suggest that either combination or sequential coupling of anti-STn therapy with conventional cytotoxic chemotherapy could target both bulk tumor and chemoresistant cells that play an important role in disease recurrence."

Ovarian cancer is the most lethal gynecologic cancer, with more than 22,400 diagnoses and over 14,000 deaths projected in 2018.1 This is due primarily to the lack of reliable early detection methods, resulting in greater than 75% of patients presenting with advanced stage disease. Unfortunately, despite aggressive surgery and adjuvant platinum-based chemotherapy with taxane, which is the standard of care2, most women with ovarian cancer develop recurrent disease that is ineffectively treated with current therapies.

"Recurrent ovarian cancer is thought to result in part from the inability to eliminate rare chemoresistant CSCs that survive cytotoxic chemotherapy and drive tumor resurgence," said Dr. Rueda. "The ability to identify markers of chemoresistant cells is central to developing new therapeutic strategies that target

these cells and ultimately provide clinical impact by reducing disease recurrence. Data from this study suggest a potential role for highly specific, glycan-targeted therapy in ovarian cancer treatment."

Siamab’s proprietary technology platform enables the development of highly specific monoclonal antibody (mAb) therapeutics, including ADCs, targeting cancer cell surface glycans called TACAs. TACAs are an emerging set of tumor-specific antigens implicated in immune suppression, chemoresistance and a CSC phenotype. The presence of STn on tumors is associated with metastatic disease, poor prognosis, and reduced overall survival.

The paper entitled, "Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau," can be found online on the Oncotarget website.

Vaxart Appoints Dr. David Taylor as Chief Medical Officer

On May 1, 2018 Vaxart, Inc., a clinical-stage biotechnology company developing oral recombinant vaccines that are administered by tablet rather than by injection, reported the appointment of David Taylor, M.D., as Chief Medical Officer. Dr. Taylor brings over 35 years of extensive experience in medical research, drug and vaccine development and clinical trial management for government organizations, non-profits, academia and both private and public healthcare companies (Press release, Vaxart, MAY 1, 2018, View Source [SID1234525899]).

"Strengthening our leadership team with the appointment of David is an important milestone for Vaxart as we continue to advance our oral vaccine platform. Dr. Taylor is a drug discovery and development veteran with deep industry knowledge developing recombinant and enteric vaccines, with expertise in the design, execution and analysis of norovirus and influenza vaccine clinical trials," said Wouter Latour, chief executive officer of Vaxart. "We are pleased to welcome David and are confident his guidance will prove invaluable as we move our vaccine programs further in the clinic."

Prior to joining Vaxart, Dr. Taylor served as a senior medical officer of the drug and vaccine development global programs at PATH, where he developed clinical trial designs and executed studies for seasonal and universal flu vaccines and enteric vaccines. Earlier, he was senior medical director of vaccines at Takeda Vaccines, developing clinical trial plans for norovirus and dengue vaccines. Previously, Dr. Taylor served as chief medical officer at VaxInnate Corporation, where he focused on the development of recombinant vaccines for influenza and other infectious diseases, and chief medical officer and vice president of medical and safety at Salix Pharmaceuticals, where he developed Rifaximin (Xifaxan) for the treatment of traveller’s diarrhea and headed medical affairs and pharmacovigilance.

Before Salix, he was a research professor for the Department of International Health at Johns Hopkins Bloomberg School of Public Health. Dr. Taylor began his career as an epidemic intelligence service officer in the Enteric Disease Branch at the Centers for Disease Control and Prevention (CDC) and served 22 years in various capacities at research institutes in the United States Army including founder and chief of the Department of Clinical Trials and acting director for the Division of Communicable Diseases and Immunology at the Walter Reed Army Institute of Research.

Dr. Taylor earned his MSc. in Medical Parasitology from the London School of Hygiene and Tropical Medicine, M.D. from Harvard Medical School, D.M.S. from Dartmouth Medical School and B.S. in Biology from Kenyon College.

About Vaxart

Obsidian to Present Data on Regulated Cytokine Programs at the Upcoming American Society of Gene and Cell Therapy (ASGCT) 21st Annual Meeting

On May 1, 2018 Obsidian Therapeutics, Inc., a biotechnology company dedicated to the development of next-generation cell and gene therapies with pharmacologic operating systems, reported that two abstracts highlighting preclinical data on the use of its technology for regulation of immunocytokines have been selected for presentation at the 21st Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper), taking place May 16-19, 2018, in Chicago, IL (Press release, Obsidian Therapeutics, MAY 1, 2018, View Source [SID1234525898]).

Details of the poster presentations, both taking place on Wednesday, May 16, 2018, are as follows:

Poster Title: Exogenous In Vitro and In Vivo Regulation of Interleukin-12 Secretion from T Cells Using Destabilizing Domain Technology
Presenter: Dexue Sun
Session Date/Time: Wednesday May 16, 2018, at 5:30 – 7:30 p.m. CT
Session title: Cancer – Immunotherapy, Cancer Vaccines I
Room: Stevens Salon C, D
Abstract number: 113

Poster Title: Dose dependent exogenous regulation of membrane bound Interleukin-15-Interleukin-15 receptor alpha fusion protein for adoptive T-cell therapy
Presenter: Christopher Reardon
Session Date/Time: Wednesday May 16, 2018, at 5:30 – 7:30 p.m. CT
Session title: Cancer – Targeted Gene & Cell Therapy I
Room: Stevens Salon C, D
Abstract number: 133

About Destabilizing Domains

Obsidian uses Destabilizing Domains (DDs) to enable pharmacologic regulation of protein activity for next-generation cell and gene therapies. Obsidian’s DDs are small, fully-human protein domains that confer conditional stability to a fused payload protein. In the absence of a specific small molecule ligand the fusion protein is rapidly degraded, whereas in the presence of the ligand, the fusion protein becomes stable and functional. Obsidian uses this approach to equip engineered cells with controllable functions that can be precisely tuned by the administration of non-immunosuppressive, small molecule medicines that are readily available and dispensed by the treating physician.

Ironwood Pharmaceuticals Provides First Quarter 2018 Investor Update

On May 1, 2018 Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD), a commercial biotechnology company, reported on its first quarter 2018 results and recent business activities (Press release, Ironwood Pharmaceuticals, MAY 1, 2018, View Source;p=irol-newsArticle&ID=2345875 [SID1234525897]).

"Ironwood’s first quarter results reflect year-over-year topline growth of 33%, significant commercial and pipeline progress, and continued financial discipline," said Peter Hecht, chief executive officer of Ironwood. "LINZESS continued to demonstrate strong demand, with 15% year-over-year prescription volume growth. We believe we have alignment on Phase III design for IW-3718 following a productive end of Phase II meeting with the FDA and expect to initiate the IW-3718 trials in the third quarter of 2018. In addition, we continue to make good progress advancing our four Phase II trials with praliciguat and olinciguat, our lead clinical sGC stimulators."

First Quarter 2018 and Recent Highlights

Irritable Bowel Syndrome with Constipation (IBS-C) / Chronic Idiopathic Constipation (CIC)

U.S. LINZESS. U.S. net sales, as reported by Ironwood’s U.S. collaboration partner Allergan plc, were $159.3 million in the first quarter of 2018, an 8% increase compared to the first quarter of 2017. Ironwood and Allergan share equally in brand collaboration profits.
LINZESS commercial margin was 63% in the first quarter of 2018 compared to 52% in the first quarter of 2017.
Net profit for the LINZESS U.S. brand collaboration, net of commercial and research and development (R&D) expenses, was $88.8 million in the first quarter of 2018, a 43% increase compared to the first quarter of 2017.
Total LINZESS prescription volume in the first quarter of 2018 included approximately 30 million LINZESS capsules, an 15% increase in capsules compared to the first quarter of 2017, per IQVIA.
More than 764,000 total LINZESS prescriptions were filled in the first quarter of 2018, an approximately 9% increase compared to the first quarter of 2017, per IQVIA.
Since the launch of LINZESS in December 2012, greater than 2 million unique patients have filled approximately 10.6 million prescriptions, per IQVIA.
In January 2018, Ironwood and Allergan reached an agreement with wholly-owned subsidiaries of Sun Pharmaceutical Industries Ltd. (Sun Pharma, including its subsidiaries and/or associated companies), resolving patent litigation brought in response to Sun Pharma’s abbreviated new drug application (ANDA) seeking approval to market a generic version of LINZESS prior to the expiration of the companies’ patents. Pursuant to the terms of the settlement, Ironwood and Allergan will grant the wholly-owned subsidiaries of Sun Pharma a license to market a generic version of LINZESS in the U.S. beginning on February 1, 2031 (subject to U.S. FDA approval), unless certain limited circumstances, customary for settlement agreements of this nature, occur. As a result of the settlement, all Hatch-Waxman litigation between the companies and Sun Pharma regarding LINZESS patents has been dismissed.
Additional Abdominal Symptom Claims. Ironwood and Allergan expect to initiate a single Phase III trial with LINZESS in mid-2018 to evaluate its efficacy for relief of additional abdominal symptoms, including bloating and discomfort, two highly bothersome symptoms associated with IBS-C.
Linaclotide Delayed Release. An estimated 20 to 25 million patients suffer from IBS-mixed and IBS with diarrhea in the U.S. Ironwood and Allergan plan to advance into a Phase IIb clinical trial a linaclotide delayed release formulation as a potential visceral, non-opioid, pain-relieving agent for patients suffering from all subtypes of IBS. The companies are in active discussions with the U.S. FDA about this program.
LINZESS-Japan. Ironwood reported $5.4 million in sales of linaclotide active pharmaceutical ingredient (API) to its Japanese partner, Astellas Pharma Inc. in the first quarter of 2018.
Uncontrolled Gout

DUZALLO (lesinurad and allopurinol) and ZURAMPIC (lesinurad). Ironwood is systematically exploring a more comprehensive marketing mix for its lesinurad franchise, including DUZALLO and ZURAMPIC, in select test markets (with paired controls), while continuing to expand affordable access across the country. The data received from these test markets in 2018 are expected to inform our lesinurad franchise investment decisions. Combined U.S. net sales were $0.6 million in the first quarter of 2018.
Persistent Gastroesophageal Reflux Disease (GERD)

IW-3718. Ironwood is actively working to advance IW-3718, its gastric retentive formulation of a bile acid sequestrant for the potential treatment of persistent GERD, into Phase III trials. There are an estimated 10 million Americans who suffer regularly from symptoms of persistent GERD, such as heartburn and regurgitation, despite receiving treatment with the current standard of care, proton pump inhibitors.
Following a series of productive meetings with the U.S. FDA, Ironwood expects to initiate two randomized, placebo-controlled Phase III trials for IW-3718 in the third quarter of 2018. These trials are expected to evaluate the safety and efficacy of IW-3718 1500mg in patients with persistent GERD. The two trials are expected to enroll less than 800 patients each, with heartburn severity response as the primary endpoint. Further details on study design and endpoints will be provided upon the initiation of the trials.
Diabetic Nephropathy and Heart Failure with Preserved Ejection Fraction (HFpEF)

Praliciguat (IW-1973). Ironwood is enrolling patients in Phase II tirals to evaluate praliciguat, its lead soluble guanylate cyclase (sGC) stimulator, for the potential treatment of serious diseases, including diabetic nephropathy and HFpEF. Both diseases affect millions of patients around the world, including an estimated eight million Americans suffering from diabetic nephropathy and an estimated three million Americans suffering from HFpEF. Diabetic nephropathy is the leading cause of end-stage renal disease. There are few treatment options available to delay the steady decline of renal function leading to dialysis or kidney transplant. HFpEF is a highly symptomatic condition with high rates of morbidity and mortality, with no approved treatments available.
Diabetic nephropathy. Ironwood expects to enroll approximately 150 patients into a randomized, double-blind, placebo-controlled, dose-ranging Phase II trial designed to evaluate the safety and efficacy of praliciguat in patients with diabetic nephropathy.
HFpEF. Ironwood expects to enroll approximately 325 patients into a randomized, double-blind, placebo-controlled, dose-ranging Phase II trial designed to evaluate the safety and efficacy of praliciguat in patients with HFpEF.
Sickle Cell Disease and Achalasia

Olinciguat (IW-1701). Ironwood is enrolling patients in Phase II trials to evaluate olinciguat, its second clinical sGC stimulator, for the potential treatment of sickle cell disease and of achalasia. Sickle cell disease is a rare, debilitating genetic disorder that affects approximately 100,000 Americans and causes red blood cells to become sickle-shaped, reducing normal red blood cell number. Achalasia is a rare disease with a prevalence rate of 10/100,000 Americans in which the lower esophagus does not relax normally, causing dysphagia (swallowing problems), regurgitation, and chest pain.
Sickle Cell Disease. Ironwood expects to enroll approximately 80 patients into a multicenter, randomized, double-blind, placebo-controlled, dose-ranging Phase II trial of olinciguat in patients with sickle cell disease. The Phase II trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of olinciguat in these patients.
Achalasia. Ironwood continues to enroll patients into a randomized, double-blind, placebo-controlled, single-dose Phase IIa study of olinciguat in patients with achalasia. This study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of olinciguat in these patients. Data from this study are expected in 2018.
Corporate and Financials

Total Revenues
Total revenues were $69.2 million in the first quarter of 2018 compared to $52.2 million in the first quarter of 2017. Included in total revenues was $61.2 million associated with Ironwood’s share of the net profits from the sales of LINZESS in the U.S., $5.4 million in sales of linaclotide API to Astellas, $0.6 million in ZURAMPIC and DUZALLO product revenue, and $2.0 million in linaclotide royalties, co-promotion and other revenue.
Operating Expenses
Operating expenses were $105.0 million in the first quarter of 2018, compared to $91.8 million in the first quarter of 2017. Operating expenses in the first quarter of 2018 included $2.6 million in cost of revenues, $36.5 million in R&D expenses, $61.9 million in selling, general and administrative (SG&A) expenses, of which $2.4 million related to Ironwood’s field-based workforce reduction in January 2018, $3.5 million in acquired intangible assets amortization expenses, and a $0.5 million loss on fair value remeasurement of contingent consideration.
Contingent consideration and amortization of acquired intangible assets relate to Ironwood’s license agreement with AstraZeneca for the exclusive U.S. rights to all products containing lesinurad.
Other Expense
Interest Expense. Net interest expense was $8.6 million in the first quarter of 2018, primarily in connection with the $150 million 8.375% Notes funded in January 2017 and the approximately $336 million convertible debt financing funded in June 2015. Interest expense recorded in the first quarter of 2018 includes $5.0 million in cash expense and $4.2 million in non-cash expense.
Gain on Derivatives. Ironwood recorded a gain on derivatives related to the change in fair value of the convertible note hedges and note hedge warrants issued in connection with the convertible debt financing funded in June 2015. A gain on derivatives of $1.3 million was recorded in the first quarter of 2018.
Net Loss
GAAP net loss was $43.1 million, or $0.29 per share, in the first quarter of 2018, compared to a net loss of $52.5 million, or $0.36 per share, in the first quarter of 2017.
Non-GAAP net loss was $40.5 million, or $0.27 per share, in the first quarter of 2018, compared to $48.3 million, or $0.33 per share, in the first quarter of 2017. Non-GAAP net loss excludes the impact of mark-to-market adjustments on the derivatives related to Ironwood’s convertible debt, as well as the amortization of acquired intangible assets and the fair value remeasurement of contingent consideration related to Ironwood’s U.S. lesinurad license. See Non-GAAP Financial Measures below.
Cash Position
Ironwood ended the first quarter of 2018 with approximately $194.4 million of cash, cash equivalents and available-for-sale securities. Ironwood used approximately $30.9 million of cash for operations during the first quarter of 2018.
Non-GAAP Financial Measures
The company presents non-GAAP net loss and non-GAAP net loss per share to exclude the impact of net gains and losses on the derivatives related to our convertible notes that are required to be marked-to-market, as well as the amortization of acquired intangible assets and the fair value remeasurement of contingent consideration associated with Ironwood’s U.S. license agreement with AstraZeneca for the exclusive rights to all products containing lesinurad. The derivative gains and losses may be highly variable, difficult to predict and of a size that could have a substantial impact on the company’s reported results of operations in any given period. The acquired intangible assets are valued as of the date of acquisition and are amortized over their estimated economic useful life, and management believes excluding the amortization of acquired intangible assets provides more consistency with the treatment of internally developed intangible assets for which research and development costs were previously expensed. The contingent consideration balance is remeasured each reporting period, and the resulting change in fair value impacts the company’s reported results of operations. The changes in the fair value remeasurement of contingent consideration do not correlate to the company’s actual cash payment obligations in the relevant period. Management believes this non-GAAP information is useful for investors, taken in conjunction with Ironwood’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to Ironwood’s operating performance. These measures are also used by management to assess the performance of the business. Investors should consider these non-GAAP measures only as a supplement to, not as a substitute for or as superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. For a reconciliation of these non-GAAP financial measures to the most comparable GAAP measures, please refer to the table at the end of this press release.

Conference Call Information
Ironwood will host a conference call and webcast at 8:30 a.m. Eastern Time on Tuesday, May 1, 2018 to discuss its first quarter 2018 results and recent business activities. Individuals interested in participating in the call should dial (877) 643-7155 (U.S. and Canada) or (914) 495-8552 (international) using conference ID number 9859406. To access the webcast, please visit the Investors section of Ironwood’s website at www.ironwoodpharma.com at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required. The call will be available for replay via telephone starting at approximately 11:30 a.m. Eastern Time, on May 1, 2018 running through 11:59 p.m. Eastern Time on May 8, 2018. To listen to the replay, dial (855) 859-2056 (U.S. and Canada) or (404) 537-3406 (international) using conference ID number 9859406. The archived webcast will be available on Ironwood’s website for 14 days beginning approximately one hour after the call has completed.

Spectrum Pharmaceuticals Enters into a Next-Generation Sequencing Companion Diagnostic Partnership with Thermo Fisher Scientific

On May 1, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported it has entered into an agreement with Thermo Fisher Scientific to leverage the Oncomine Dx Target Test as a companion diagnostic for Spectrum’s novel pan-HER inhibitor, poziotinib, which is in development for the treatment of non-small lung cancer (NSCLC) patients with EGFR and HER2 exon 20 insertion mutations (Press release, Spectrum Pharmaceuticals, MAY 1, 2018, View Source [SID1234525894]).

"Spectrum is committed to precision medicine for unmet medical needs in oncology," said Tom Riga, Executive Vice President, Chief Operating and Commercial Officer of Spectrum Pharmaceuticals. "Thermo Fisher pioneered next-generation sequencing as the first multi-drug companion diagnostic for patients with non-small cell lung cancer when Oncomine Dx Target Test received premarket approval by the FDA in June 2017. Therefore, we believe Thermo Fisher will be an outstanding partner to help us advance the development of poziotinib. As promising clinical data continue to emerge with poziotinib for the treatment of patients with EGFR and HER2 exon 20 insertion mutations, the expansion of Oncomine Dx Target Test will aid in faster detection and future treatment of patients who are not well-served by currently available therapies."

Oncomine Dx Target Test is FDA approved to simultaneously report 23 genes clinically associated with NSCLC. Of those 23, three contain markers that are approved for use as companion diagnostics, enabling physicians to match patients to three FDA-approved therapies in days instead of weeks. The test uses Thermo Fisher’s proprietary Ion PGM Dx sequencing platform to interrogate patient samples with high reproducibility and rapid turnaround times, even when limited tumor tissue is available.

Under the terms of the collaboration agreement, the goal of the expanded use of the Oncomine Dx Target Test is to identify NSCLC patients with EGFR or HER2 exon 20 insertion mutations who may be candidates for treatment with poziotinib in Spectrum’s global territories.

"We are pleased to partner with Spectrum Pharmaceuticals to help advance its drug development program and expand the clinical utility of Oncomine Dx Target Test," said Joydeep Goswami, president of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher Scientific. "We remain committed to help drive better health outcomes for patients who can benefit from targeted therapies more quickly."

About Poziotinib

Poziotinib is a novel, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum received exclusive license to develop, manufacture, and commercialize worldwide excluding Korea and China from Hanmi Pharmaceuticals. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.