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OncoSec Reports Updated Tumor Responses in KEYNOTE-695 Study of TAVO™ + KEYTRUDA® in Refractory Metastatic Melanoma

On December 12, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing novel cancer immunotherapies, reported an update regarding tumor responses in its KEYNOTE-695 global, multicenter Phase 2b, open-label trial of intratumoral delivery of TAVO (tavokinogene telseplasmid / IL-12) with intravenous KEYTRUDA (pembrolizumab) in patients with unresectable, advanced melanoma (Press release, OncoSec Medical, DEC 12, 2018, View Source [SID1234532030]). The Company previously reported at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 33rd Annual Meeting (SITC) (Free SITC Whitepaper) that, of the first nine patients to complete 12 weeks of treatment and reach initial tumor evaluation (by RECIST v1.1), two patients had a partial response. The Company now reports that both responses have been confirmed by blinded independent review at the first assessment timepoint. Further, in both cases, response duration has now reached six months. Importantly, one of these previously assessed partial responses has now become a complete response per investigator assessment at the six-month tumor evaluation timepoint. Enrollment is ongoing and the Company expects to complete the study next year.

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"Complete responses in this patient population are rare. One of the first partial responses to be observed in this study now being assessed by the investigator at six months as a complete response is exciting. Durable responses reaching the six-month mark demonstrate that the benefits of TAVO are clinically meaningful," said Daniel J. O’Connor, President and CEO of OncoSec. "The evidence of the potential of TAVO in conjunction with PD-1 inhibition to improve outcomes in this patient population is mounting and we look forward to providing updates as necessary regarding the progress of this trial."

KEYNOTE-695 enrollment criteria with respect to anti-PD-1 checkpoint failure is highly restrictive. In order to be considered an anti-PD-1 checkpoint failure, all patients must have Stage III/IV metastatic melanoma progressive disease after at least four prior cycles of either KEYTRUDA or OPDIVO. Literature suggests that retreatment with a PD-1 therapy following failure of a PD-1 therapy offers approximately a 5% response rate1. Disease progression is determined according to RECIST v1.1, measured by radiologic assessment, with confirmation of progression by second assessment.

"It’s becoming clear that TAVO can reverse PD-1 resistance in refractory metastatic melanoma patients. This is important because the majority of melanoma patients do not respond to PD-1 treatment," said Adil Daud, MD, HS Clinical Professor, Department of Medicine (Hematology/Oncology), UCSF; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center and Lead Principle Investigator of KEYNOTE-695. "Patients in KEYNOTE-695 have unequivocally failed all approved anti-PD-1 therapies. The tumor responses seen in this trial, now independently verified by a blinded review at the first assessment, deepening and continuing for months, gives us confidence in the potential of this treatment combination for patients who are non-responsive to anti-PD-1 therapy."

Eligible patients in KEYNOTE-695 had refractory, locally advanced or metastatic disease defined as unresectable Stage III/IV metastatic melanoma that had definitively progressed on a full-course of anti-PD-1 treatment with KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab). As previously reported, TAVO was well-tolerated, with primarily Grade 1 adverse advents associated with injection site or procedural pain. One TAVO related Grade 3 SAE of cellulitis was reported and resolved. KEYNOTE-695 is expected to be completed in 2019. Based on the outcome of the study, the Company plans to file for accelerated approval by end of 2019 or early 2020.

TAVO has received both Orphan Drug and Fast-Track Designation by the U.S. Food & Drug Administration.

1 Long GV, Weber JS, Larkin J et al. Nivolumab for patients with advanced melanoma treated beyond progression: analysis of 2 Phase 3 clinical trials. JAMA Oncol. 3(11), 1511–1519 (2017).

MediciNova to Present at the J.P. Morgan Healthcare Conference in San Francisco

On December 12, 2018 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that Yuichi Iwaki, MD, PhD, President and Chief Executive Officer, and Geoffrey O’Brien, JD/MBA, Vice President and Executive Officer, will present a corporate overview at the J.P. Morgan Healthcare Conference on Wednesday, January 9, 2019 at 2:00 pm at the Westin St. Francis Hotel in San Francisco, California (Press release, MediciNova, DEC 12, 2018, View Source;p=irol-newsArticle&ID=2380360 [SID1234532029]). MediciNova’s management team, including Dr. Yuichi Iwaki, Geoffrey O’Brien, and Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer, will be available for one-on-one meetings at this conference and investors may request a one-on-one meeting through J.P. Morgan.

Santhera Announces Financial Results for the First Nine Months of 2018

On December 12, 2018 Santhera Pharmaceuticals (SIX: SANN) reported its financial results for the nine months ended September 30, 2018, and confirms its guidance and positive outlook (Press release, Santhera Pharmaceuticals, DEC 12, 2018, View Source [SID1234532027]).

Santhera is on track to meet its strategic and financial goals for 2018. The Company further delivered on its active in-licensing strategy for high quality, late-stage rare disease assets by acquiring an exclusive sub-license option to vamorolone, the first-in-class dissociative steroid currently in development for the treatment of Duchenne muscular dystrophy (DMD). On the commercial side, the Company has further grown sales of the revenue-generating product Raxone for the treatment of Leber’s hereditary optic neuropathy (LHON) and expects to meet its 2018 full-year sales guidance in the range of CHF 30-32 million.

Santhera continued its business expansion and grew sales to CHF 23.6 million in the first nine months of 2018 which corresponds to a 45% growth rate (compared to the same period in the previous year). Development expenses increased by 49% compared to the same prior-year period, primarily driven by clinical development activities for POL6014 for the treatment of cystic fibrosis (CF) and regulatory work in preparation of filings for idebenone in the indication DMD. Efficient use of resources resulted in lower marketing and sales expenses (-6%) and a slower rise in general and administrative expenses (+18%). Taken together, this contributed to an increase of operating expenses by 20% compared to the same period of last year. In summary, Santhera closed the nine-month period under review with a net result of CHF -39.9 million (Jan.-Sept. 2017: CHF -33.3 million).

Financial highlights:

Sales of CHF 23.6 million (Jan.-Sept. 2018), reflecting an increase by 45% compared to same period last year (Jan.-Sept. 2017: CHF 16.3 million)
Operating expenses of CHF 57.2 million (Jan.-Sept. 2017: CHF 47.7 million)
Operating result of CHF -37.2 million (Jan.-Sept. 2017: CHF -34.2 million), leading to a net result of CHF -39.9 million (Jan.-Sept. 2017: CHF -33.3 million)
Cash, cash equivalents and short-term financial assets of CHF 25.4 million (as of September 30, 2018)
2018 full-year sales guidance of CHF 30-32 million confirmed
Corporate highlights:

Agreement with Idorsia Ltd under which Santhera is to acquire the option to an exclusive sub-license of the first-in-class dissociative steroid vamorolone in all indications and all countries worldwide except Japan and South Korea (November 20, 2018)
Idorsia became largest shareholder in Santhera
Extraordinary General Meeting (EGM) approval of the capital increase in connection with the vamorolone sub-license agreement (December 11, 2018)
Operational highlights (July 2018 to present day):

Analysis of new data linking study findings with idebenone in DMD to clinically relevant patient benefits for inclusion in regulatory submissions in Europe and the U.S.
Positive opinion on orphan drug designation received from European regulators for POL6014 for the treatment of CF
Start of a Phase Ib/IIa multiple ascending dose (MAD) trial with POL6014 in patients with CF
Revenue Guidance:
Santhera will continue to grow its international business, advance its pipeline programs and actively proceed with business development initiatives to expand its late stage product portfolio. Based on its sales performance to date this year, the Company confirms its previous guidance and expects to reach a full-year sales for Raxone in the range of CHF 30-32 million in 2018.

Note
The financial statements as of and for the nine months ended September 30, 2018 have been prepared and are being published exceptionally on the occasion of and in connection with the capital increase proposed to and approved by the EGM held on December 11, 2018. Santhera publishes results in line with the disclosure requirements of the SIX Swiss Exchange. Santhera does not plan on publishing quarterly reports in the future.

Oncolytics Biotech® Announces First Patient Treated in Study Combining Pelareorep, Carfilzomib and the Checkpoint Inhibitor Opdivo® in Multiple Myeloma

On December 12, 2018 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that the first patient was treated in a phase 1 dose escalation study combining pelareorep and carfilzomib with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) to treat relapsed multiple myeloma patients (Press release, Oncolytics Biotech, DEC 12, 2018, View Source [SID1234532025]). This study is based on findings from the NCI 9603 multiple myeloma study that combined pelareorep with carfilzomib that resulted in objective responses, elimination of multiple myeloma cells and most importantly, an inflamed phenotype with PD-L1 overexpression.

"Having worked with pelareorep in multiple myeloma and understanding its ability to act as a potentiator of checkpoint blockade, I’m very excited to work with the Oncolytics team on this study," said Dr. Craig Hofmeister, Associate Professor, Department of Hematology and Medical Oncology Emory University School of Medicine. "Pelareorep has proven its ability to create an inflamed phenotype and its potential for upregulation of PD-1 on tumor-infiltrating lymphocytes. My hope is this study leads not only to an effective combination dosing schedule but provides quantitative data describing the expression of PD-1, along with correlative studies that reveal the roles of both immune-mediated and direct cytotoxic myeloma cell killing."

This open-label, phase 1 study, conducted by Dr. Hofmeister at Emory University, will enroll up to 62 patients to examine the side effects and best dosing schedule of pelareorep when given in combination with dexamethasone, carfilzomib, and nivolumab in treating participants with relapsed multiple myeloma. The primary objectives of the study are to determine the maximum tolerated dose of pelareorep in combination with carfilzomib and nivolumab. Secondary outcome measures include time to progression, progression-free survival and overall survival, as well as the characterization of an inflamed phenotype and confirmation of biomarker responses indicative of tumor inflammation.

"We now have our second checkpoint inhibitor combination study enrolling, and I’m excited for the potential of the immune and biomarker data to come from it," said Dr. Rita Laeufle, Chief Medical Officer of Oncolytics Biotech. "These studies, along with our soon to be initiated studies combining pelareorep with Merck’s Keytruda, also in multiple myeloma, and Roche’s Tecentriq in neoadjuvant breast cancer, will provide further evidence that pelareorep has the potential to expand the use of checkpoint inhibitors by priming tumors cells. The confirmation of our predictive biomarkers enhances the likelihood of success in registrational studies, thereby reducing both clinical and commercial risk making pelareorep more attractive to potential partners."

For more information about the study, including a comprehensive list of inclusion and exclusion criteria, please visit: www.clinicaltrials.gov (identifier: NCT03605719).

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

Aptose Presents Highlights From CG-806 KOL Event

On December 12, 2018 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) reported highlights from a Key Opinion Leader (KOL) breakfast featuring a presentation by Brian Druker, M.D., Professor of Medicine at the School of Medicine at Oregon Health & Science University (OHSU), Director of OHSU’s Knight Cancer Institute, and Aptose management team (Press release, Aptose Biosciences, DEC 12, 2018, View Source [SID1234532023]).

The webcast of the presentation will be archived on Aptose’s website here.

William G. Rice, Ph.D., Chairman, President and Chief Executive Officer, first provided a recap on CG-806, Aptose’s highly potent pan-FLT3/pan-BTK inhibitor, and included the following key highlights:

CG-806 has a well-differentiated mechanism of action, selectively and potently inhibiting kinase clusters that include all forms of FLT3 and BTK, as well as rescue pathways that can allow resistance to other drugs, and avoiding other kinase clusters associated with toxicity
CG-806 demonstrated superior potency on acute myeloid leukemia (AML) patient cells relative to all other FLT3 inhibitors
CG-806 demonstrated superior potency on B-cell patient cells relative to ibrutinib
In preclinical mouse model studies, CG-806 induced rapid and sustained tumor eradication with no observed toxicity
CG-806’s safety profile remains clean: New results, recently presented at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting from 28-day GLP toxicity and toxicokinetic studies, continue to demonstrate a highly favorable safety profile with no adverse findings to date
Dr. Druker discussed the evolution of kinase inhibitors as anticancer drugs, reviewed the current treatment landscape in AML and B-cell cancers, emphasizing the medical needs for these patient populations, and highlighted his experience with CG-806 alone and in combination to potentially address these medical needs. Key highlights:

CG-806 potently killed primary malignant cells from patients with diverse hematologic malignancies
CG-806 demonstrated superior killing potency on cells from AML patients compared to five other FLT3 inhibitors
AML patient cells with the FLT3-ITD mutation, found in approximately 30% of AML patients, were highly sensitive to CG-806
Just presented at ASH (Free ASH Whitepaper), AML patient cells with the IDH-1 mutation were unexpectedly sensitive to CG-806, a new finding that further broadens CG-806’s potential use and potential paths for rapid development
CG-806 data demonstrated broad and superior killing potency compared to ibrutinib, which is the current standard of care for B-cell malignancies, on cells from patients with CLL and other B-cell cancers
Drug combination studies with CG-806 and venetoclax on patient bone marrow cells suggest the combination may become the preferred drug combination for patients with AML, CLL, ALL and other hematologic malignancies
"CG-806 is unlike any molecule we have investigated, and it is more than just a FLT3 and BTK inhibitor," said Dr. Druker. "806 has the unusual ability to suppress key driver and rescue pathways and overcome the resistance that develops with other kinase inhibitors, and it has demonstrated potent activity against actual primary cells from patients with hematologic malignancies. We are hopeful that clinical testing will prove it to be a new treatment for a patient population in need of new options."

Stephen B. Howell, M.D., Professor of Medicine at the University of California, San Diego, and Associate Director for Clinical Research at the Moores UCSD Cancer Center, who serves as Aptose’s Acting Chief Medical Officer, wrapped up the prepared remarks of the session with current development plans for CG-806:

IND-enabling GLP toxicology and safety studies with CG-806 are complete
As a result of its robust safety profile, Aptose plans to file an IND in the first quarter of 2019 to begin clinical testing of CG-806 both in healthy volunteers (HVS) and in patients with B-cell malignancies
After a therapeutic dose is identified from the HVS or B-cell malignancy clinical trials, Aptose intends to expand into acutely ill AML patients and other sensitive subpopulations
About CG-806
CG-806 is a preclinical stage oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. It is in development for acute myeloid leukemia (AML) and B cell lymphoma.

Brian J. Druker, M.D.
Brian Druker, M.D., is the director of the Knight Cancer Institute, Associate Dean for oncology of the OHSU School of Medicine, JELD-WEN Chair of Leukemia Research and a Howard Hughes Medical Institute investigator. He revolutionized the treatment of cancer through research that resulted in the development of imatinib, the first drug to target the molecular defect of a cancer while leaving healthy cells unharmed. Marketed under the name Gleevec, his discovery turned a once-fatal cancer, chronic myeloid leukemia, into a manageable condition. This work changed the life expectancy of patients with CML from an average of 3 to 5 years to a 95% five-year survival, and has resulted in a paradigm-shift in cancer treatment from non-specific chemotherapy to highly targeted therapeutic agents. He is a member of the National Academy of Medicine, the National Academy of Sciences and, among numerous awards, is the recipient of the 2009 Lasker-DeBakey Clinical Medical Research Award and most recently, the 2018 Tang Prize in Biopharmaceutical Science.

Dr. Druker currently serves as the Chair of the Scientific Advisory Board for Aptose. He receives compensation from Aptose for this role. He and his team at OHSU, through the BEAT AML collaboration, have directly conducted studies with CG-806 on fresh bone marrow samples from patients with various hematologic malignancies, and data from these studies serve as the cornerstone of presentations made by Aptose Biosciences.