On March 26, 2018 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company announced the presentation of maturing data from the TOPACIO trial of niraparib in combination with an anti-PD-1 monoclonal antibody, KEYTRUDA during a plenary session today at the 2018 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in New Orleans, Louisiana. In addition, retrospective data analyses of the Phase 3 ENGOT-OV16/NOVA study that could potentially reduce Grade 3/4 thrombocytopenia in niraparib treated patients was presented in the plenary session on Sunday, March 25 (Press release, TESARO, MAR 26, 2018, View Source [SID1234525015]).

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"Patients with platinum-resistant or platinum-refractory ovarian cancer have limited treatment options available to them. Approximately 10,000 women in each of the US and EU begin treatment for platinum-resistant or refractory ovarian cancer each year," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Preliminary results from TOPACIO suggest the combination of niraparib and an anti-PD-1 antibody could provide meaningful clinical benefit to these patients, regardless of biomarker status. Planning of a registration study is underway to support approval of ZEJULA and TSR-042 combination therapy for these patients. TSR-042 is TESARO’s anti-PD-1 antibody, which is currently in a registration study for MSI-H tumors."

"These data provide a compelling initial step in our ovarian cancer development strategy which is progressing from monotherapy ZEJULA utilized in PRIMA, NOVA and QUADRA to doublet and triplet combination approaches with anti-PD-1 antibodies and bevacizumab," said Marty Huber, M.D., Senior Vice President and Chief Medical Officer of TESARO. "Our ultimate goal is to maximize the benefit to women across the full spectrum of ovarian cancer"

Phase 2 TOPACIO Data Demonstrate Activity in Platinum-Resistant and Platinum-Refractory Ovarian Cancer Patients, Regardless of Biomarker Status
TOPACIO is a Phase 1/2 clinical trial designed to evaluate the safety and efficacy of niraparib plus KEYTRUDA (pembrolizumab) in patients with recurrent, platinum-resistant ovarian cancer or triple negative breast cancer. Niraparib administered orally, once-daily, at a dose of 200 milligrams is being evaluated in combination with 200 milligrams of pembrolizumab administered intravenously on day one of each 21-day treatment cycle in two patient cohorts; platinum-resistant/refractory ovarian cancer and triple-negative breast cancer. Endpoints include RECIST response rate, duration of response, disease control rate, progression-free survival and overall survival. Data presented at SGO were from the group of patients with ovarian cancer.

At the time of data cutoff, of the 62 patients enrolled, 60 were evaluable; 45% had been treated with 3 or more prior lines of chemotherapy, 97% with prior taxane, 63% received prior bevacizumab, and 29% were platinum refractory. The majority (73%) did not have a BRCA mutation. Data indicate an overall response rate (ORR; including CR and PR) of 25% and a disease control rate (DCR; CR+PR+SD) of 68%; ORR was 24% in the platinum refractory population. Response rates were not dependent on biomarker status; ORR was 26% (9/34) in patients without a tumor BRCA mutation (tBRCAwt), and 29% (7/24) in patients with HRD-negative tumors. Duration of response was immature, with 9 of 15 (60%) of responders remaining on treatment, and over one-half of patients with disease control continuing on treatment or having already received treatment for over 6 months.

For patients with platinum-resistant ovarian cancer, response to chemotherapy is 5-18%, including the most commonly prescribed regimen in the U.S., bevacizumab plus pegylated liposomal doxorubicin1. Platinum refractory patients typically have even lower response rates and NCCN treatment guidelines recommend clinical trials for these patients2. Historical response to PARP inhibitors is 5-10% in patients without BRCA mutations who have platinum resistant disease3 and 0-14% in those with BRCA mutations and platinum refractory disease4. Response rates of 10-15% have been reported with anti-PD-1 antibodies in this ovarian cancer population5.

The combination of niraparib with pembrolizumab was well tolerated with an incidence of Grade 3/4 thrombocytopenia of 9%. In addition to thrombocytopenia, the other most commonly observed Grade ≥3 adverse events included anemia (19%) and neutropenia (6%).

Abstracts containing additional data from the TOPACIO trial, including results from patients with platinum-resistant ovarian cancer and patients with triple-negative breast cancer, have been submitted to the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The TOPACIO trial is being conducted in collaboration with Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc., which is providing support for the trial.

A Retrospective Analysis of Phase 3 ENGOT-OV16/NOVA Trial Identified Predictors of Early Dose Modification for Niraparib
A retrospective analysis of the Phase 3 NOVA trial identified two baseline characteristics, patient body weight less than 170 pounds (77 kilograms) or platelet count of <150,000/µL to be significant factors for Grade 3 or 4 thrombocytopenia. The incidence of thrombocytopenia in the first month in this population was 35% in the NOVA study vs 12% in those with higher weight and platelet counts. By month 4, of the patients who remained on treatment, 83% with body weight < 170lbs or platelet count of <150,000/µL at baseline were receiving a dose of niraparib <300 milligrams. With dose interruptions, this group’s average daily dose was 207 milligrams in the first two months of niraparib therapy in NOVA. Regardless, efficacy was uncompromised (HR: 1.01 (95%CI: 0.69, 1.48)) in patients receiving a 200 milligram versus 300 milligram dose of niraparib. Of note, in TOPACIO, where starting dose is 200 milligrams, a 9% incidence of Grade 3 or 4 thrombocytopenia was reported.

"This analysis provides physicians with new information to help quickly identify the most appropriate dose for each of their patients," said Dr. Mansoor Raza Mirza, M.D., Medical Director of the Nordic Society of Gynecologic Oncology (NSGO) and principal investigator on the ENGOT-OV16/NOVA trial. "This information is particularly important as we move towards combination treatment approaches with niraparib, which are currently being studied in multiple ongoing clinical trials."

About ZEJULA (Niraparib)
Niraparib is marketed in the United States and Europe under trade name ZEJULA. ZEJULA (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in some clinical studies. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.

About TSR-042

TSR-042 is a monoclonal antibody targeting PD-1 and was developed as part of the collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3 (TSR-075).

On March 26, 2018 RXi Pharmaceuticals Corporation (NASDAQ: RXII) a biotechnology company developing immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform today reported its financial results for the fourth quarter and year ended December 31, 2017, and provided a business update (Press release, RXi Pharmaceuticals, MAR 26, 2018, View Source [SID1234525014]).

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"In early 2018, RXi announced a strategic decision to solely focus its development efforts on novel immuno-oncology treatments based on its self-delivering RNAi platform. We have made good progress by entering in development collaborations with some major cancer research centers in Europe and in the US. The first results from these collaborations are promising and support our goals to enter into clinical testing in the coming 12 to 18 months," said Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. He further added, "RXi is well-positioned for success with the potential to match and possibly surpass current antibody treatments by exploiting the self-delivering attributes of our therapeutic compounds for immuno-oncology using an adoptive cell transfer approach. As outlined in January of this year, RXi is seeking to monetize our dermatology and ophthalmology assets through out-licensing or partnerships for which we have achieved proof of concept in clinical trials, as such demonstrating the significant therapeutic potential of our self-delivering RNAi platform. The success of this initiative should provide additional non-dilutive means to advance our ongoing internal programs and external collaborations for our immuno-oncology pipeline and prepare for entering the clinic in 2019."

The Company will host a conference call today at 5:00 p.m. EST to discuss financial results and provide an update on the Company. The webcast link will be available under the "Investors – Event Calendar" section of the Company’s website, www.rxipharma.com. The event may also be accessed by dialing toll-free in the United States: +1 (844) 376-4678. International participants may access the event by dialing: +1 (209) 905-5958. An archive of the webcast will be available on the Company’s website approximately two hours after the presentation.

Select Fourth Quarter and Fiscal 2017 Financial Highlights

Cash

At December 31, 2017, the Company had cash of $3.6 million as compared with $12.9 million at December 31, 2016.

On August 8, 2017, the Company entered into a purchase agreement with Lincoln Park Capital Fund, LLC ("LPC"), pursuant to which the Company has the right to sell to LPC up to $15 million in shares of the Company’s common stock, subject to certain limitations and conditions set forth therein, over the 30-month term of the purchase agreement. To date, the Company has sold a total of 285,000 shares of common stock to LPC for net proceeds of approximately $1.2 million.

Revenues

In September 2017, the Company’s collaborative partner BioAxone Biosciences, Inc. received a grant award from the National Institute of Neurological Disorders and Stroke. BioAxone has been awarded a total of $1,794,895 to fund the collaborative project over 24 months. For our contribution, RXi will receive approximately $129,000 in the first year with the potential to receive an additional $118,800 in the second year after achieving certain milestones. The two-year grant provides funding for further development of BioAxone’s preclinical candidate BA-434, a novel sd-rxRNA compound that targets PTEN for the treatment of spinal cord injury.

Revenues for the quarter ended December 31, 2017 were $15,000. The Company had no revenue during the quarter ended December 31, 2016. Revenues for the year ended December 31, 2017 were $15,000, as compared with $19,000 for the year ended December 31, 2016. Revenues for the quarter and year ended December 31, 2017 were due to the work performed by the Company under the grant with BioAxone. Revenues for the year ended December 31, 2016 were due to the Company’s exclusive out-licensing agreements with MirImmune, prior to its acquisition by the Company, and Thera Neuropharma, Inc.

Research and Development Expenses

Research and development expense for the quarter ended December 31, 2017 was $1.2 million, as compared with $1.3 million for the quarter ended December 31, 2016. The decrease was due to lower spending on clinical trial-related expenses as subject visits in each of the Company’s ongoing clinical trials came to an end.

Research and development expense for the year ended December 31, 2017 was $5.4 million, as compared with $5.4 million for the year ended December 31, 2016. Overall, expenses were consistent year over year despite an increase in direct research and development expenses due to the addition of the immuno-oncology program to the Company’s development pipeline in the first quarter of 2017 with the acquisition of MirImmune, which was offset by a decrease in non-cash stock-based compensation expense.

Acquired In-process Research and Development

In January 2017, the Company acquired all of the issued and outstanding capital stock of MirImmune Inc., a privately-held biotechnology company that was engaged in the development of cancer immunotherapies, in exchange for securities of the Company. The aggregate fair value of the consideration given, which includes transaction costs, liabilities assumed and cancellation of notes receivable, and the deferred tax impact of the acquisition was recorded as in-process research and development expense.

Acquired in-process research and development expense related to the acquisition of MirImmune was $5.0 million for the year ended December 31, 2017. The Company did not have acquired in-process research and development expense for the three months ended December 31, 2017 and 2016 and the year ended December 31, 2016.

General and Administrative Expenses

General and administrative expense for the quarter ended December 31, 2017 was $0.8 million, as compared with $1.0 million for the quarter ended December 31, 2016. The decrease was due to a reduction in mailing and printing-related fees for the Company’s annual meeting, which last year was held in the December time-frame, as well as a reduction in professional fees for legal services and employee-related expenses as compared to the prior year quarter.

General and administrative expense for the year ended December 31, 2017 was $4.0 million, as compared with $3.6 million for the year ended December 31, 2016. The increase was primarily due to payroll-related expenses, including severance benefits, related to the Company’s former Chief Business Officer and professional fees for legal-related services.

Income Tax

The Company recognized an income tax benefit of $1.6 million for the year ended December 31, 2017 due to the tax-related impact of the Company’s acquisition of MirImmune Inc. The Company did not have income tax expense or benefit for the three months ended December 31, 2017 and 2016 and the year ended December 31, 2016.

Net Loss Applicable to Common Stockholders

Net loss applicable to common stockholders for the quarter ended December 31, 2017 was $2.0 million, compared with $4.4 million for the quarter ended December 31, 2016. The decrease was due to the one-time charge related to the beneficial conversion feature of the Company’s Series B Convertible Preferred Stock in 2016.

Net loss applicable to common stockholders for the year ended December 31, 2017 was $12.5 million, compared with $11.1 million for the year ended December 31, 2016. The increase was primarily driven by acquired in-process research and development expense incurred for the acquisition of MirImmune, offset by the one-time charge related to the beneficial conversion feature of the Company’s Series B Convertible Preferred Stock in 2016.

Nasdaq Compliance

On January 23, 2018, the Company received written notice from the Nasdaq Stock Market, LLC notifying the Company that it had regained compliance with the minimum bid price requirement for continued listing on The Nasdaq Capital Market. The written notice was sent following the implementation of the Company’s 1-for-10 reverse split of the Company’s common stock, which became effective on January 8, 2018. At the effective time of the reverse stock split, every ten shares of RXi common stock was combined into one share of common stock, reducing the Company’s issued and outstanding common stock from 24.3 million shares to 2.4 million shares.

Select Fourth Quarter 2017 and Recent Corporate Highlights

Select Business and Corporate Highlights

Immuno-Oncology

RXi Pharmaceuticals developed a robust self-delivering RNAi-based technology platform, termed sd-rxRNA, a key value driver unique to RXi. The robust technology platform provides a strong foundation that we have leveraged to build a leading Immuno-oncology company, with a short-term focus using Adoptive Cell Transfer (ACT). sd-rxRNA offers unprecedented flexibility in targeting immunosuppressive pathways with the potential to modulate multiple checkpoint genes in a single therapeutic treatment. The built-in delivery and therapeutic properties of sd-rxRNA lend themselves well for local therapeutic applications, such as ex vivo treatment of the immune cells. The ex vivo use of sd-rxRNA to pre-treat immune cells prior to infusion may prove advantageous as an immuno-therapeutic in that there is the potential to simultaneously reduce multiple checkpoints or targets, including both intracellular and extracellular targets, with little change to current protocols.

During 2017, the Company advanced its development strategy by selecting a lead preclinical compound and commencing cGMP manufacturing to prepare for the initiation of a clinical trial in 2019. In addition, the Company entered into a number of partnerships across the globe to expand its pipeline, which include:

1. PCI Biotech: A collaboration is underway with this biopharmaceutical company located in Norway, to evaluate technology compatibilities and synergies between our respective technology platforms for the potential applicability of combination therapy in immuno-oncology.

2. Gustave Roussy: This leading Comprehensive Cancer Centre in Europe is evaluating the potential of RXi’s novel sd-rxRNA technology platform for use in cancer treatments.

3. Center for Cancer Immune Therapy (CCIT) at Herlev Hospital: Based in Denmark, CCIT is a leading European center evaluating the potential of the sd-rxRNA technology platform in TILs for the use in treatment for a number of cancer types, including melanoma and ovarian cancer.
4. Medigene AG: A German based biotechnology company is exploring potential synergies of using sd-rxRNA in combination with Medigene’s recombinant TCRs to develop modified T cells with enhanced efficacy and/or safety.
To further support these efforts, RXi appointed two leading oncology experts to its Scientific Advisory Board (SAB). RXi’s new SAB members are Dr. Rolf Kiessling, Professor in Experimental Oncology at Karolinska Institutet and Senior Chief Physician of Radiumhemmet at Karolinska Hospital as well as medical oncology expert Dr. James D. Griffin, Chairman, Department of Medical Oncology, Dana-Farber Cancer Institute. Dr. Griffin also serves as Professor, Medicine, Harvard Medical School and Director, Medical Oncology, Brigham and Women’s Hospital.

The Company also added additional strategic business development and immuno-oncology expertise to its Board of Directors through the appointment of Dr. Jonathan Freeman. Dr. Freeman is an established leader with positions spanning from Senior Vice President, Head of Strategy Development and Portfolio Management at Merck KGaA to a number of senior positions at Baxter and Serono, in M&A and, Corporate and Business Development, respectively.

In addition to the expansion of our SAB and Board of Directors, Dr. Gerrit Dispersyn, Dr. Med. Sc. joined RXi as its Chief Development Officer in May 2017. Dr. Dispersyn is an accomplished leader and brings a wealth of experience in clinical, product and business development. He has held a number of senior leadership positions at Integra LifeSciences Corporation and Barrier Therapeutics.

Business Development Opportunities

RXi has developed two robust therapeutic Franchises in Dermatology and Ophthalmology that are comprised of advanced clinical programs, robust discovery assets and substantial Intellectual Property rights. RXi added to its broad patent estate with the granting of a patent from the Japan Patent Office (JPO) in Q1 207 for the composition of matter of sd-rxRNAs targeting connective tissue growth factor (CTGF) for the treatment or prevention of fibrotic disorders, including but not limited to skin fibrosis and proliferative retinopathy (Japanese Patent #: 6060071), which includes RXI-109.

The Company has an active process underway to monetize these assets which will support a return on investment for stockholders and accelerated growth in the immuno-oncology focus area.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as "intends," "believes," "anticipates," "indicates," "plans," "expects," "suggests," "may," "should," "potential," "designed to," "will" and similar references, although not all forward-looking statements contain these words. Forward-looking statements are neither historical facts

nor assurances of future performance. These statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially from those indicated in the forward-looking statements as a result of a number of important factors, including those identified in our most recent Annual Report on Form 10-K under the caption "Risk Factors" And in other filings the Company periodically makes with the Securities and Exchange Commission. Readers are urged to review these risk factors and to not act in reliance on any forward-looking statements, as actual results may differ from those contemplated by our forward-looking statements. RXi does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release.

On March 26, 2018 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported 2 year recurrence rate data from the Phase 2 trial evaluating HS-410 (vesigenurtacel-L) in combination with standard of care, Bacillus Calmette-Guérin (BCG), for the treatment of non-muscle invasive bladder cancer (NMIBC) (Press release, Heat Biologics, MAR 26, 2018, View Source [SID1234524990]). As previously announced, the Company discontinued its HS-410 program in order to focus its resources on current and future checkpoint combination trials, including its HS-110 Phase 2 lung cancer program in combination with Bristol-Myers Squibb’s checkpoint inhibitor nivolumab. However, in keeping with clinical trial guidance, Heat continued to monitor all patients enrolled in the study for a 2-year duration.

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Within the subgroup of patients who received the low dose of Heat’s ImPACT HS-410 with standard of care BCG and who demonstrated a positive immune response, 10 out of 10 (100%) remained disease-free after a 2-year period. A positive immune response was defined as 2-fold or greater increase from baseline of CD8+ T cells in peripheral blood as measured by ELISPOT analysis.

Jeff Wolf, Heat’s CEO, commented, "We are further encouraged by this latest data in immune responders showing a 100% disease-free survival rate over 2 years, in the subgroup of patients that received low-dose HS-410 and BCG. The observed clinical benefit is consistent with our recent data in non-small cell lung cancer where we reported that patients who have robust immune responses as measured by ELISPOT analysis, have improved survival benefit, providing further support for the mechanism of action of our unique gp96-based T-cell Activation Platform. Heat is committed to the development of its therapeutic programs in combination with a PD-1/PD-L1 inhibitor, as we believe this provides us the best opportunity for a sustained, activated CD8+ T-cell response."

Jeff Hutchins, Heat’s Chief Scientific Officer, further commented, "We believe the future of immuno-oncology therapy will be built on a multipronged, orchestrated attack: polyclonal T-cell activation, clonal T-cell expansion and checkpoint inhibition. Most importantly, we believe the ability to mount a robust poly T-cell activated immune response has the potential to improve clinical outcomes. We are encouraged by the correlation of clinical benefit and immune responses linked to our gp96-based poly-neoantigen T-cell activation platform in these two different cancer settings."

Heat recently reported positive interim results from its Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), in patients with advanced non-small cell lung cancer (NSCLC).

On March 26, 2018 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the company has completed the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring an NTRK gene fusion (Press release, Loxo Oncology, MAR 26, 2018, View Source [SID1234524992]).

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"We are grateful to the many patients who participated in our clinical trials in the spirit of helping others with advanced cancer," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We hope that the larotrectinib development program inspires others to develop drugs for both adult and pediatric patients on the basis of tumor genetics rather than tumor site of origin."

Loxo Oncology and Bayer are engaged in a collaboration for the development and commercialization of larotrectinib. A Marketing Authorisation Application (MAA) submission by Bayer in the European Union is expected in 2018.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and highly selective tropomyosin receptor kinase (TRK) inhibitor. The investigational new drug is in clinical development for the treatment of patients with cancers that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In clinical trials, larotrectinib demonstrated marked and durable anti-tumor activity in TRK fusion cancer regardless of patient age or tumor type. In an analysis of 55 RECIST-evaluable adult and pediatric patients with NTRK gene fusions, larotrectinib demonstrated an 80 percent investigator-assessed confirmed overall response rate (ORR) and a 75 percent centrally-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib was well tolerated; the majority of all adverse events were grade 1 or 2. There were no treatment-related grade 4 or 5 events, and no treatment-related grade 3 adverse events occurred in more than 5% of patients.

Larotrectinib has been granted Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA.

In November 2017, Loxo Oncology and Bayer entered into an exclusive global collaboration for the development and commercialization of larotrectinib and LOXO-195, a next-generation TRK inhibitor. Bayer and Loxo Oncology will jointly develop the two products with Loxo Oncology leading the ongoing clinical studies as well as the filing in the U.S., and Bayer leading ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Loxo Oncology and Bayer will co-promote the products.

For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About TRK Fusion Cancer
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled tropomyosin receptor kinase (TRK) signaling that can lead to cancer. NTRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. NTRK gene fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC), to detect TRK protein. For more information, please visit www.trkcancer.com.

On March 26, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported that new clinical safety data from the expansion phase of a Phase 2 clinical trial at the Bone Marrow Failure Disease Scientific Symposium, held in Rockville, Maryland, on March 22-23, 2018 (Press release, Onconova, MAR 26, 2018, View Source [SID1234524993]).

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Oral rigosertib has been developed as a single agent and in combination with azacitidine. Previous studies have demonstrated that Low-Risk (LR) MDS patients with intermittent oral rigosertib treatment at a dose of 560 mg BID show a transfusion independence rate (TI), as defined by the IWG 2006 criteria, of 44% (Raza, et al, Blood 2017 130:1689). Oral rigosertib in combination with AZA is being studied in patients with Higher-risk (HR) MDS. Initial results of the Phase 2 study with oral rigosertib (840 mg /day 3 out of 4 weeks) in combination with azacitidine in patients with MDS demonstrated an overall response rate of 76%; 62% in patients following hypomethylating agent (HMA) failure; and 85% in HMA naïve patients (Navada et al, EHA (Free EHA Whitepaper), 2017). In both single agent and combination studies, oral rigosertib has been associated with hematuria in a subset of patients which has been shown to be dose and administration scheme dependent (Garcia-Manero G, Blood 2016 128:2011). The results reported here are from a dose exploration study in HR MDS patients with an increased oral rigosertib dose (1120 mg/day 3 out of 4 weeks) and focus on the impact of risk-mitigation strategies in minimizing the incidence of urinary adverse events (UAEs); including hematuria. The mitigation strategies included prescribing the second dose of rigosertib earlier in the day and encouraging bladder emptying at bedtime.

The reported incidence of hematuria of any grade with single agent azacitidine is 6.3%, including 2.3% grade 3 and 4 events (per product insert). In the combination trial of oral rigosertib (total dose of 840 mg/day 3 out of 4 weeks) and azacitidine, the incidence of hematuria was 48%, with grade 3 or grade4 AEs of 12%. In the new study, in 37 patients studied with oral rigosertib (total dose of 1120 mg/day 3 out of 4 weeks) and azacitidine employing prophylactic risk-mitigating strategies to minimize hematuria, a significantly lower incidence of grade 1 & 2 hematuria (11%), and no grade 3 or 4 hematuria have been seen to date.

Guillermo Garcia-Manero, M.D, Professor and Chief of the MDS Section at the MD Anderson Cancer Center, who presented the new results, commented, "Choices are very limited for higher risk MDS, with two HMAs as the only drugs approved by the Health Authorities for these patients. There is an urgent need to develop novel approaches, including combination therapies that can improve the outcomes in patients who require an HMA. The previously presented studies of the combination regimen of oral rigosertib with azacitidine have demonstrated impressive evidence of efficacy in HMA naïve and HMA refractory patients with higher-risk MDS. Since the success of a combination therapy is greatly influenced by the safety and tolerability of the regimen, the new results of improved tolerability are of great importance for the proposed pivotal study of this combination. The ability to ensure longer duration of treatment without interruption or dose reduction due to an acceptable safety profile can ensure optimal benefit for patients. We look forward to participating in the planned Phase 3 study of this novel approach, which combines two agents with distinct mechanisms of action for the potential benefit of frontline MDS patients."

Dose optimization and risk mitigation strategies undertaken specifically to minimize UAEs associated with oral rigosertib in combination with azacitidine have resulted, to date, in a decrease in frequency of hematuria from 48% to 11% and elimination of any serious grade 3 events. Minimization of AEs permits patients to continue on treatment to optimize the potential benefit. Reduction in incidence of hematuria also enables the continued study of oral rigosertib in LR-MDS, based on the promising TI Rate previously reported.

A copy of the poster is available by visiting the Scientific Presentations section of Onconova’s website.