On November 5, 2019 Cotinga Pharmaceuticals Inc. (TSX Venture: COT; OTCQB: COTQF) ("Cotinga" or the "Company"), a clinical-stage pharmaceutical company advancing a pipeline of targeted therapies for the treatment of cancer, reported that it has entered into a research collaboration with St. Vincent’s University Hospital in Dublin, Ireland to evaluate COTI-2 in combination with eribulin in patients with triple negative metastatic breast cancer (Press release, Cotinga, NOV 5, 2018, View Source [SID1234533149]).

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"Cotinga is committed to the development of therapies for a wide range of cancers, and our collaboration with St. Vincent’s University Hospital represents an important step towards realizing the full potential of our lead compound, COTI-2," said Dr. Richard Ho, M.D., Ph.D., Chief Scientific Officer. "Throughout this year we presented preclinical and early clinical results that support COTI-2 as a possible combination therapy, and this partnership with St. Vincent’s will allow us to further explore how COTI-2 may work alongside the standard of care in cancers with severe unmet medical need."

The Phase 1 study will aim to evaluate COTI-2 in combination with eribulin in the second or subsequent line therapy of patients with triple negative metastatic breast cancer. The primary objectives of the study will be to determine the optimal tolerated dose of COTI-2 that can be added to standard dose eribulin in the second or subsequent line treatment of metastatic breast cancer, and to assess the safety and tolerability of COTI-2 when administered with eribulin.

"Triple-negative metastatic breast cancer is a serious and difficult-to-treat disease that tends to be more aggressive than other types of breast cancer," said Professor John Crown, M.D., M.B.A., consultant medical oncologist at St. Vincent’s University Hospital. "Our research demonstrates that the p53 gene is mutated in approximately 80% of triple-negative tumors, and suggests that mutant p53 has potential as a therapeutic target. We are encouraged by early data from COTI-2, which targets mutant p53, and having seen synergy in our own preclinical testing of COTI-2 and eribulin, we look forward to evaluating the compound in combination with standard of care for patients with triple negative metastatic breast cancer."

On November 5, 2018 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported the initiation of its global, multi-center, registration-directed trial of tipifarnib in HRAS mutant head and neck squamous cell carcinomas (HNSCC) (Press release, Kura Oncology, NOV 5, 2018, View Source [SID1234530720]).

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"We are excited to announce that our first registration-directed trial is now underway," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "Prior to our experience, tipifarnib was studied in more than 5,000 patients and although it demonstrated compelling anti-cancer activity in some cases, no molecular target was identified that could explain such activity. This registration-directed trial implements the many learnings from our clinical experience in patients with HNSCC. We believe we can now identify those patients most likely to receive clinical benefit from tipifarnib. If successful, we believe this registration-directed trial could bring a much-needed treatment option to patients with HRAS mutant HNSCC."

About the Registration-Directed Trial

Kura’s registration-directed clinical trial is a global, multi-center study of tipifarnib in HRAS mutant HNSCC. The open-label trial has two cohorts: AIM-HN, a treatment cohort, and SEQ-HN, a non-interventional screening and outcomes cohort.

AIM-HN is designed to enroll at least 59 patients with HRAS mutant HNSCC who have received prior platinum-based therapy, and is expected to take approximately two years to fully enroll. Based on observations from Kura’s Phase 2 trial, patients in AIM-HN must have a tumor HRAS mutant allele frequency of at least 20%. Enrolled patients will receive a starting dose of 600 mg of oral tipifarnib, twice daily, on days 1-7 and 15-21 of 28-day treatment cycles. The trial’s primary endpoint is objective response rate (ORR), as determined by independent radiological review. Secondary outcome measures will include overall survival, duration of response, progression free survival and time to response.

AIM-HN has approximately 80% power to detect a difference between a null hypothesis of 15%, which is the point estimate of the ORR of second-line therapy for recurrent and metastatic disease, and 30%, an ORR considered of interest. Based on feedback from the U.S. Food and Drug Administration (FDA), Kura believes that AIM-HN, if positive, may be adequate to support a new drug application (NDA) seeking accelerated approval.

SEQ-HN is an observational cohort and is designed as a case-control study, matching patients with recurrent or metastatic HNSCC with HRAS mutations against those who are HRAS wild type using factors such as age, line of therapy and type of treatment. SEQ-HN is expected to provide a better understanding of the natural history of patients with HRAS mutations while contributing to identify patients for potential enrollment into AIM-HN. HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified may enroll into SEQ-HN.

Additional information about the trial can be found at clinicaltrials.gov using the identifier NCT03719690.

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is an inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown compelling and durable anti-cancer activity in certain patient subsets. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, the Company is seeking to identify those patients most likely to benefit from tipifarnib. In addition to its development program in solid tumors with HRAS mutations, Kura has identified the CXCL12 pathway and bone marrow homing of myeloid cells as potential biomarkers of activity for tipifarnib in certain hematologic malignancies. The Company plans to present preliminary data from the angioimmunoblastic T-cell lymphoma (AITL) and CXCL12+ expansion cohorts in a Phase 2 trial of tipifarnib in peripheral T-cell lymphomas (PTCL) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.

On November 5, 2018 Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology company focused on developing and commercializing innovative gene therapy products for patients living with serious, life-threatening rare diseases, reported that Co-Founder and Chief Executive Officer (CEO) Matthew R. Patterson has been appointed Chairman of the Board of Directors (Press release, Audentes Therapeutics, NOV 5, 2018, View Source [SID1234530738]). The Board of Directors also appointed Louis G. Lange, M.D., Ph.D. as Lead Independent Director. Mr. Patterson and Dr. Lange have held board member roles since 2012 and 2015, respectively.

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"It is a great privilege for me to serve our company as Chairman of the Board of Directors," stated Matthew R. Patterson, Chairman and CEO. "Audentes is at an exciting inflection point, and I look forward to working closely with the board and management team to deliver on important milestones that advance our mission of developing innovative gene therapy products for patients living with serious, life-threatening rare diseases."

Mr. Patterson continued, "I am also pleased to announce the appointment of Dr. Lange to the position of Lead Independent Director. Lou is a recognized leader in the biotechnology industry who brings a unique and valued perspective to our organization. We’re fortunate to benefit from Lou’s deep experience gained over a successful career as a physician and founder and CEO of innovative public biotechnology companies, and I look forward to partnering with him in the leadership of our board."

Mr. Patterson has more than 25 years of experience in the research, development, and commercialization of innovative treatments for rare diseases and has held positions of senior management in both private and public biotechnology companies. Previously Mr. Patterson worked for Genzyme Corporation, BioMarin Pharmaceutical, and Amicus Therapeutics. Prior to Audentes he was an Entrepreneur-In-Residence with OrbiMed, one of the world’s largest healthcare dedicated investment firms. Mr. Patterson currently serves as Chairman of the Alliance for Regenerative Medicine (ARM), the international advocacy organization representing the gene and cell therapy and broader regenerative medicine sector. He is a member of the Board of Directors for Homology Medicines, Inc., Modis Therapeutics, Inc., and Gilda’s Club of New York City, which provides support for people living with cancer. Mr. Patterson received his Bachelor’s degree in Biochemistry from Bowdoin College.

Dr. Lange was the founder of CV Therapeutics, and as the Chairman, CEO, and Chief Scientific Officer, led the company through an IPO, the approval of two first-in-class cardiovascular drugs, RANEXA and LEXISCAN, and the sale of the company to Gilead Sciences, Inc. Prior to joining industry, Dr. Lange spent 22 years in academic medicine at Harvard and Washington University, where he served as Chief of Cardiology and Professor of Medicine at Jewish Hospital and was one of the first academicians in molecular cardiology. Dr. Lange is currently a General Partner at Asset Management Ventures, serves as a senior advisor to Gilead Sciences, Inc., and has served on numerous other public and private boards in both the non-profit and for-profit sectors. Dr. Lange holds a Doctorate degree in Biochemistry from Harvard University and a Medical Doctor degree from Harvard Medical School. He earned a Bachelor’s degree from the University of Rochester.

On November 5, 2018 Kura Oncology, Inc., (Nasdaq: KURA) a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported third quarter 2018 financial results and provided a corporate update (Press release, Kura Oncology, NOV 5, 2018, View Source [SID1234530721]).

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"We are very encouraged by our growing body of data that support the potential of tipifarnib as a treatment for squamous cell carcinomas characterized by HRAS mutations," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "With our registration-directed trial of tipifarnib in HRAS mutant head and neck squamous cell carcinomas (HNSCC) now underway, we are focused on generating a data package to support an application for marketing approval in that indication, as we work to broaden the potential of tipifarnib in both HRAS mutant and non-HRAS mutant cancers. In that regard, we are encouraged by preliminary signals of clinical activity observed in patients with HRAS mutant SCCs as we believe this may represent a near-term opportunity to expand the use of tipifarnib into a broader set of HRAS mutant cancers."

"In addition," Dr. Wilson continued, "we believe the CXCL12 pathway also holds promise for identifying patients who will respond to tipifarnib, and we look forward to showing data next month at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from our ongoing Phase 2 clinical trial in patients with peripheral T-cell lymphoma (PTCL) in which we are evaluating, on a prospective basis, the role of the CXCL12 pathway and markers of bone marrow homing as potential biomarkers of clinical activity of tipifarnib."

Corporate Update

Update on positive Phase 2 trial of tipifarnib in HRAS mutant HNSCC – In October 2018, Kura reported an update on its ongoing Phase 2 trial of tipifarnib in HRAS mutant HNSCC at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress. As of the September 7, 2018 clinical data cutoff date, tumor size reductions were observed in nine of 11 evaluable patients, with five confirmed partial responses (PRs), including three patients with durable responses lasting more than 17 months. A sixth patient achieved a confirmed PR after the data cutoff. Four patients had stable disease, including two patients who experienced prolonged disease stabilization lasting more than six months. Only one patient experienced progressive disease as best response.

Preliminary results from cohort of other HRAS mutant SCCs – Preliminary results from an additional cohort of patients with other HRAS mutant squamous cell carcinomas (SCCs) were also reported at ESMO (Free ESMO Whitepaper). One of the two evaluable patients in this cohort achieved a confirmed PR and the other patient achieved prolonged disease stabilization lasting more than eight months. Four patients were not evaluable as of the data cutoff date, including two patients who were pending initial efficacy assessments.

Significant association observed between allele frequency and clinical benefit – An analysis of available tumor biopsy samples from patients in Kura’s ongoing Phase 2 trial in HNSCC/SCC cancers revealed a significant association between the allele frequency of HRAS mutations and clinical benefit. Of the 13 HNSCC and SCC patients with a tumor HRAS mutant allele frequency greater than 20%, six achieved PRs, one achieved an unconfirmed PR and two experienced disease stabilization greater than six months. No meaningful clinical benefit was observed in the seven patients with an allele frequency less than 20%. Based on these observations, Kura has introduced a minimum HRAS mutant allele frequency of 20% as an entry criterion in its registration-directed trial of tipifarnib in HRAS mutant HNSCC and is working to implement the same entry criterion in its ongoing Phase 2 study of tipifarnib in HRAS mutant SCCs.

Initiation of registration-directed trial of tipifarnib in HRAS mutant HNSCC – Earlier today, Kura announced that its registration-directed trial of tipifarnib in HRAS mutant HNSCC has been initiated and is open for enrollment. The global, multi-center trial has two cohorts: SEQ-HN, a non-interventional screening and outcomes cohort, and AIM-HN, a treatment cohort. AIM-HN is designed to enroll at least 59 patients with HRAS mutant HNSCC who have received prior platinum-based therapy. AIM-HN is expected to take approximately two years to fully enroll, with objective response rate as the primary endpoint. Based on feedback from the U.S. Food and Drug Administration, Kura believes that the trial, if positive, could support an application for accelerated approval.

Preliminary data from expansion cohorts in Phase 2 trial of tipifarnib in PTCL at ASH (Free ASH Whitepaper) – Kura is evaluating, on a prospective basis, the role of the CXCL12 pathway and markers of bone marrow homing as potential biomarkers of clinical activity for tipifarnib in various hematologic malignancies. The Company’s ongoing Phase 2 PTCL trial was the first of the three to begin and is actively enrolling patients into two cohorts: 1) patients with angioimmunoblastic T-cell lymphoma (AITL) and 2) patients with PTCL who have the absence of a single nucleotide variation in the 3’ untranslated region of the CXCL12 gene. Kura expects to provide preliminary data from these cohorts at ASH (Free ASH Whitepaper) in December 2018.
Financial Results

Research and development expenses for the third quarter of 2018 were $11.7 million, compared to $7.1 million for the third quarter of 2017.

General and administrative expenses for the third quarter of 2018 were $4.3 million, compared to $2.4 million for the third quarter of 2017.

Net loss for the third quarter of 2018 was $15.0 million, or $0.40 per share, compared to $9.3 million, or $0.38 per share, for the third quarter of 2017.

Cash, cash equivalents and short-term investments totaled $187.4 million as of September 30, 2018, compared with $93.1 million as of December 31, 2017.
Upcoming Milestones

Preliminary data from AITL and CXCL12+ cohorts in Phase 2 trial of tipifarnib in PTCL at ASH (Free ASH Whitepaper)

Additional biomarker-enriched data from other hematologic indications in 2019

Additional data from Phase 2 trial of tipifarnib in HRAS mutant SCC in 2019

Data from Phase 1 dose-escalation trial of ERK inhibitor KO-947 in 2019

Submission of an investigational new drug application for menin-MLL inhibitor KO-539 in first quarter of 2019
Conference Call and Webcast

Kura’s management will host a webcast and conference call today at 4:30 p.m. ET / 1:30 p.m. PT today, November 5, 2018, to discuss the financial results for the third quarter of 2018 and provide a corporate update. The live call may be accessed by dialing (877) 516-3514 for domestic callers and (281) 973-6129 for international callers and entering the conference code: 6593979. A live webcast of the call will be available from the Investors and Media section of the Company’s website at www.kuraoncology.com, and will be archived there for 30 days.

On November 5, 2018 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), a clinical-stage biotechnology company specializing in the development of innovative drugs in oncology targeting tumor DNA Damage Response (DDR) to fight resistant cancers, reported positive interim results from the first three dose levels already evaluated out of six planned in its Phase 1 DRIIV-1 study of AsiDNA, the Company’s first-in-class DNA Damage Response inhibitor (Press release, Onxeo, NOV 5, 2018, View Source [SID1234530739]).

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A total of 10 patients with advanced solid tumors received 112 infusions of AsiDNA ranging from 200mg (DL1) to 600mg (DL3). The administration of DL4 (900mg) is ongoing and the full data set from DRIIV-1 is expected to be available in the first half of 2019.

Judith Greciet, Chief Executive Officer of Onxeo, said: "We are very pleased to report highly compelling interim results from our DRIIV-1 study. Beyond the safety endpoints of all phase 1 studies, DRIIV-1 was foremost designed to demonstrate that AsiDNA administered intravenously activates in patients’ tumors cells the intended DNA Damage Response biological targets. Midway through the study, data show that robust target engagement was demonstrated as early as the second dose level, which represents a meaningful proof-of-mechanism of AsiDNA in man. In addition, the results indicate a favorable safety profile for AsiDNA in a difficult-to-treat patient population. These proof-of-mechanism and activity results further support the clinical potential of AsiDNA in solid tumors and represent a major value catalyst in the development of our first-in-class drug candidate."

Pharmacokinetic parameters

Both Cmax (maximal concentration) & AUC (area under the curve) data show dose proportionality from dose level 1 to dose level 3, with systemic exposure rising proportionally to the dose.

Pharmacodynamic parameters (activity data)

In accordance with the study protocol, biopsies were performed during cycle 2 of treatment with AsiDNA and analyzed by comparison with baseline biopsies. Target engagement by AsiDNA was measured by quantifying through immuno-histochemistry two established biomarkers of the activation of DNA-PK, a major target for AsiDNA, gH2AX and pHSP90.

Post-treatment biopsies were available and analyzed for four patients (two post-DL2 and two post-DL3), showing a robust activation of DNA-PKA as evidenced by a significant post-treatment increase in the quantification of these activity biomarkers in patients’ tumor tissue. These data confirmed strong target engagement and activity in tumors at these two AsiDNA dosages.

Furthermore, the quantification of a well-known tumor proliferation biomarker, Ki67, showed a clear decrease of the proliferation rate in tumors of three patients and stabilization in one patient.

Safety data

Intravenous administration of AsiDNA was generally well-tolerated at DL1, DL2 and DL3, with no drug- related serious adverse event and no dose-limiting toxicity.

Olivier de Beaumont, Chief Medical Officer of Onxeo, concluded: "We are very encouraged by these first safety and proof-of-mechanism data, which confirm the activity and tolerability of AsiDNA via systemic administration. AsiDNA is now ready to enter the next stage of its clinical development. Our translational work on the combination of AsiDNA with PARP inhibitors is indicative of the unique properties of this combination, such as the prevention, and even reversal, of the resistance to PARP inhibitors. Promising data have also been obtained in combination with DNA-damaging agents such as platins or taxanes. Combining AsiDNA with these agents will therefore be our first priority as we expand its clinical development to Phase1b/2 efficacy studies in combination in 2019. In parallel, the DRIIV-1 study is progressing to plan and we are on track to deliver full results in the first half of 2019."

Onxeo will host a conference call in English with a Q&A session for analysts and investors at 5:30 pm CET / 11:30 pm ET today to discuss this announcement

Location

Phone number

France +33 1 72 72 74 03
United States +1 646 722 4916
United Kingdom +44 20 7194 3759
Denmark +45 8233 3187

Participation code: 33251686#

Access to the management presentation prior to the call

An audio replay file will be made available after the session on Onxeo’s website.
About the DRIIV-1 study

DRIIV-1 (DNA Repair Inhibitor administered IntraVenously) is an open-label, dose escalation, Phase 1 study evaluating the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNA via systemic (IV) administration in patients with advanced solid tumors. The study is being conducted at leading oncology centers in France and Belgium.

Six dose levels (DLs) are planned (DL1 to DL6): 200mg, 400mg, 600mg, 900mg, 1,300mg and 1,800mg. All patients receive a loading dose of AsiDNA for 3 consecutive days (1-hour IV infusion at day 1, day 2 and day 3), followed by a one-hour IV infusion once a week (at day 8 and day 15) of a 21 days treatment period (1 cycle = 21 days). In each subsequent cycle, AsiDNA is administered on a weekly basis (day 1, day 8 and day 15) of a 21 days treatment period. Patients are continuing study treatment until disease progression, unacceptable toxicity or patient’s refusal to continue.

Each dose level is stepped up following validation by a Data Safety Monitoring Board.

The primary objective is to determine dose-limiting toxicities and maximum tolerated dose of IV infusion of AsiDNA. Secondary objectives are to assess the safety profile, PK parameters and target engagement of AsiDNA based on the quantification of activity biomarkers in tumor tissue (YH2AX, pHSP90). In addition, proliferation tumor status as measured by KI67 immunostaining, and preliminary efficacy of AsiDNA, are also being evaluated.