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OncoGenex Pharmaceuticals, Inc. and Achieve Life Science, Inc. Announce Definitive Merger Agreement

On January 5, 2017 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) ("OncoGenex"), a publicly held oncology biopharmaceutical company, and Achieve Life Science, Inc. ("Achieve"), a privately held specialty pharmaceutical company, reported that they have entered into a definitive merger agreement under which OncoGenex will acquire Achieve in an all-stock transaction (Press release, OncoGenex Pharmaceuticals, JAN 5, 2017, View Source [SID1234517294]).

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Upon completion of the proposed merger, Achieve’s equity holders are expected to own 75% of the combined company’s outstanding shares and current stockholders of OncoGenex are expected to own the remaining 25% of the combined company’s outstanding shares. Following completion of the merger, OncoGenex Pharmaceuticals, Inc. will be renamed Achieve Life Sciences, Inc.

In addition, prior to the completion of the proposed merger, OncoGenex is expected to distribute to its stockholders contingent value rights (CVRs) for 80% of any net proceeds of certain payments arising from a future sale, transfer, license or similar transaction involving OncoGenex’s apatorsen oncology product candidate.

The combined company’s executive management team will be led by Rick Stewart, Chairman of Achieve; Anthony Clarke, Chief Scientific Officer of Achieve; John Bencich, Chief Financial Officer of OncoGenex; and Cindy Jacobs, Chief Medical Officer of OncoGenex. The combined company plans to utilize select clinical and corporate resources from OncoGenex’s existing operations to accelerate the clinical development program of cytisine for smoking cessation. The board of directors of the combined company is expected to consist of seven members, four of which will be designated by Achieve and three of which will be designated by OncoGenex.

The proposed merger will create a clinical-stage company focused on clinical and commercial development of cytisine, a selective nicotine receptor partial agonist currently in late-stage development for smoking cessation. Two recent Phase 3 trials in over 2,000 patients using cytisine as a smoking cessation aid have been completed, with positive results published in the New England Journal of Medicine. In total, over 10,000 individuals have now participated in clinical trials evaluating cytisine. The product is currently marketed by a third party in Central and Eastern Europe and is believed to have treated in excess of 20 million patients.

In addition to cytisine, the combined company’s pipeline will also include apatorsen (OGX-427), a once-weekly intravenous drug designed to inhibit production of heat shock protein 27 (Hsp27) to disable cancer cells’ defenses and overcome treatment resistance. Positive Phase 2 results were recently reported following final analysis of the Borealis-2 trial of apatorsen in combination with docetaxel treatment that enrolled 200 patients with metastatic bladder cancer whose disease had progressed following first-line platinum-based chemotherapy. Patients who received apatorsen treatment experienced a 20% reduction in risk of death, compared to patients receiving docetaxel alone (HR=.80; 95% CI: 0.65-0.98; p=0.078). Efforts will continue to establish a strategic partnership to further the development of apatorsen.

"After extensive and thorough review of strategic alternatives, we are very pleased to announce this proposed merger with Achieve as it adds both immediate and long-term product opportunities in indications with significant patient need and commercial opportunity," said Scott Cormack, President and CEO of OncoGenex. "With cytisine in late-stage development for smoking cessation and having a defined regulatory path with FDA, we believe the proposed merger provides our stockholders with an opportunity to realize value from their investment in OncoGenex."

Rick Stewart, Chairman of Achieve, added, "Achieve is expecting to meet a number of significant clinical and regulatory milestones within the next 12-18 months culminating in a final, large-scale Phase 3 clinical trial. The merger of OncoGenex and Achieve provides additional clinical and corporate resources to meet those milestones."

The transaction has been approved unanimously by the boards of directors of both companies. The proposed merger is expected to close by mid-2017, subject to customary closing conditions.

MTS Health Partners is acting as exclusive financial advisor to OncoGenex and Fenwick & West LLP is acting as legal counsel. Paul Hastings LLP is acting as legal counsel to Achieve.

Important Additional Information about the Proposed Merger

This communication is being made in respect of the proposed merger involving OncoGenex Pharmaceuticals, Inc. and Achieve Life Science, Inc. OncoGenex will file with the Securities and Exchange Commission, or SEC, a current report on Form 8-K, which will include the merger agreement and related documents. In addition, OncoGenex intends to file a registration statement on Form S-4 with the SEC, which will contain a joint proxy statement/prospectus and other relevant materials, and plans to file with the SEC other documents regarding the proposed transaction. The final joint proxy statement/prospectus will be sent to the stockholders of OncoGenex and Achieve. The joint proxy statement/prospectus will contain information about OncoGenex, Achieve, the proposed merger, and related matters. STOCKHOLDERS ARE URGED TO READ THE JOINT PROXY STATEMENT/PROSPECTUS (INCLUDING ANY AMENDMENTS OR SUPPLEMENTS) AND OTHER DOCUMENTS FILED WITH THE SEC CAREFULLY IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE, AS THEY WILL CONTAIN IMPORTANT INFORMATION THAT STOCKHOLDERS SHOULD CONSIDER BEFORE MAKING A DECISION ABOUT THE MERGER AND RELATED MATTERS. In addition to receiving the joint proxy statement/prospectus and proxy card by mail, stockholders will also be able to obtain the joint proxy statement/prospectus, as well as other filings containing information about OncoGenex, without charge, from the SEC’s website (View Source) or, without charge, by directing a written request to: OncoGenex Pharmaceuticals, Inc., 19820 North Creek Parkway, Suite 201, Bothell, WA 98011, Attention: Investor Relations or to Achieve Life Science, Inc., 30 Sunnyside Avenue, Mill Valley, CA 94941, Attention: Rick Stewart.

This communication shall not constitute an offer to sell or the solicitation of an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities in connection with the proposed merger shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933, as amended.

Participants in Solicitation
OncoGenex and its executive officers and directors may be deemed to be participants in the solicitation of proxies from OncoGenex’s stockholders with respect to the matters relating to the proposed merger. Achieve and its officers and directors may also be deemed a participant in such solicitation. Information regarding OncoGenex’s executive officers and directors is available in OncoGenex’s proxy statement on Schedule 14A, filed with the SEC on April 21, 2016. Information regarding any interest that OncoGenex, Achieve or any of the executive officers or directors of OncoGenex or Achieve may have in the transaction with Achieve will be set forth in the joint proxy statement/prospectus that OncoGenex intends to file with the SEC in connection with its stockholder vote on matters relating to the proposed merger. Stockholders will be able to obtain this information by reading the joint proxy statement/prospectus when it becomes available.

About Achieve and Cytisine
Achieve is developing cytisine as a smoking cessation aid. Cytisine is a plant-based alkyloid with a high binding affinity to the nicotinic acetylcholine receptor. It is an established smoking cessation treatment that has been approved and marketed in Central and Eastern Europe for more than 15 years. It is estimated that over 20 million people have used cytisine to help combat nicotine addiction, including approximately 2,000 patients in Phase 3 clinical trials conducted in Europe and New Zealand. Achieve’s focus is to address the global smoking health epidemic, which is currently the leading cause of preventable death and responsible for nearly six million people losing their lives annually worldwide. Discussions have been held with FDA and a European regulatory agency to determine the clinical and regulatory pathway towards making cytisine widely available.

Trethera Corporation and Nanotherapeutics Sign Exclusive Worldwide Agreement for Rights to Triapine® in Hematological Malignancies

On January 5, 2017 Trethera Corporation and Nanotherapeutics, Inc. reported the signing of an exclusive worldwide agreement whereby Nanotherapeutics has granted Trethera an exclusive license for the global development, manufacturing and marketing of Triapine (3-AP) and all formulations, for the treatment of hematological malignancies (Press release, Nanotherapeutics, JAN 5, 2017, View Source [SID1234517286]). Triapine is a clinical-stage, small molecule inhibitor of ribonucleotide reductase (RNR), a key enzyme in the de novo pathway of nucleotide biosynthesis.

Trethera has advanced preclinical development of proprietary, small molecule inhibitors of deoxycytidine kinase (dCK), the rate-limiting enzyme in the salvage pathway of nucleotide biosynthesis. Results of its preclinical studies indicate robust and durable anti-leukemic activity of its dCK inhibitors when combined with inhibitors of RNR, and these combinations have demonstrated superior activity over single agent treatments. Trethera aims to commence a Phase I clinical trial for its orally administered, lead dCK inhibitor, TRE-515, in H2 2017.

"This license agreement marks an important step in addressing the needs of patients and physicians combating acute leukemia as well as other blood cancers," said Johanna Holldack, MD, Chief Executive Officer and President of Trethera Corporation. "Our recent non-clinical studies indicate how powerful the combination of Triapine and TRE-515 could be. Securing this partnership accelerates our development pathway and ensures that the potential of this pioneering combination therapy will be fully realized."

Prasad Raje, Ph.D., President and Chief Executive Officer of Nanotherapeutics, commented, "We are delighted to be able to license Triapine to Trethera for the treatment of hematological malignancies. Trethera’s scientific team is pursuing critically important research which may unlock this compound’s ability to yield new blood cancer therapies in the future and we look forward to watching their progress."

Stemline Therapeutics Announces Positive FDA Meeting and Agreement on Expedited Pathway to Full Approval of SL-401 in First-Line BPDCN

On January 5, 2017 Stemline Therapeutics, Inc. (Nasdaq:STML) reported an agreement with the U.S. Food and Drug Administration (FDA) on the registration pathway for SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Stemline Therapeutics, JAN 5, 2017, View Source [SID1234517283]). To support the filing of a Biologics License Application (BLA) for full approval in first-line BPDCN, Stemline is currently enrolling an additional small cohort, planned for 8-12 first-line BPDCN patients, into its ongoing Phase 2 trial. To date, approximately half of these new patients are enrolled into the study, with full enrollment expected this quarter. Stemline intends to file a BLA in 2H17, which is anticipated to undergo an expedited review given SL-401’s Breakthrough Therapy Designation. If successful, Stemline projects a commercial launch of SL-401 in 2018.

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We are extremely pleased with the outcome of our meeting with the FDA and the Agency’s continued guidance regarding SL-401, which was granted Breakthrough Therapy Designation this past August. The Agency has now provided us with a clear and potentially rapid pathway to obtain full approval of SL-401 in first-line BPDCN, as well as the possibility for review in the relapsed/refractory setting. We are actively enrolling patients who are to be included in the final cohort of the trial and are targeting completion of enrollment this quarter." Dr. Bergstein continued, "In parallel, our operations and regulatory teams are working hard to ensure a timely and comprehensive BLA filing, including addressing additional data requests from the Agency, while our commercial team is setting the stage, if approved, for a successful launch of SL-401. Additionally, we continue to advance SL-401 into other indications in an effort to provide benefit to patients who are battling aggressive cancers."

Conference Call and Webcast
Stemline Therapeutics will host a conference call and audio webcast Friday, January 6, 2017 at 8:00 AM ET. Interested participants and investors may access the conference call by dialing 888-778-9052 (U.S./Canada) or 913-312-0850 (International) and referencing conference ID: 9093286. An audio webcast can also be accessed via the Investor Relations tab of the Stemline Therapeutics website at View Source

About Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
For more information on BPDCN, please visit Stemline’s patient and physician resource site: www.bpdcninfo.com.

Mirati Therapeutics Provides Update On Glesatinib And Sitravatinib Clinical Trials And Pipeline Programs

On January 5, 2017 Mirati Therapeutics, Inc. (Mirati or the Company) (NASDAQ: MRTX) reported data from two ongoing clinical programs, including the Phase 1b and Phase 2 trials of glesatinib, a spectrum selective kinase inhibitor for the treatment of non-small cell lung cancer (NSCLC) patients with genetic alterations of MET, and the Phase 1b trial of sitravatinib, a receptor tyrosine kinase inhibitor for the treatment of genetically-selected NSCLC and other solid tumors (Press release, Mirati, JAN 5, 2017, View Source [SID1234517282]).

"The transition to the new spray dried dispersion (SDD) formulation of glesatinib has succeeded in improving tolerability, resulting in significantly fewer formulation-specific side effects in patients with NSCLC. Early results with the SDD formulation have demonstrated promising activity in NSCLC patients with MET mutations," said Charles M. Baum, M.D., Ph.D., President and CEO of Mirati.

"We are similarly encouraged by data from our Phase 1b trial of sitravatinib, which indicate its potency in RET inhibition. Early results from the trial show clear evidence of tumor responses in NSCLC patients exhibiting RET fusion mutations."

Glesatinib Program Update
The SDD formulation of glesatinib was introduced into the Phase 1b trial and Phase 2 AMETHYST trial in May of 2016. This formulation has thus far demonstrated improved tolerability versus the prior miglyol soft gel formulation.

Patients from both Phase 1b and Phase 2 trials were assessed as of December 2, 2016 to evaluate the impact of the new SDD formulation (n=41) as compared to the prior soft gel formulation (n=50). Adverse event-related (AE-related) dose reductions occurred in 17% (7/41) of patients treated with the new SDD formulation, versus 46% (23/50) of patients treated with the prior soft gel formulation. In patients who were transitioned to the SDD formulation during their therapy (n=12), AE-related dose reductions took place in 8% (1/12) of patients versus 33% (4/12) of patients treated with the soft gel formulation.

In an initial evaluation of 24 genetically-selected patients treated with the SDD formulation of glesatinib:
11 patients were in the Phase 2 MET Exon 14 deletion mutation cohort, of whom eight were evaluable.

Eight patients were in the Phase 2 MET amplification cohort, all of whom were evaluable.

Five patients were in the Phase 1b trial with MET Exon 14 deletion mutations, who had clinical characteristics and genetic driver alterations identical to the entry criteria in the ongoing Phase 2 trial, all of whom were evaluable.

In MET Exon 14 deletion patients treated with the SDD formulation across both the Phase 1b and Phase 2 trials, glesatinib demonstrated promising activity:

In the Phase 2 trial, one confirmed partial response (PR) and two unconfirmed PRs out of the eight evaluable patients were observed. One unconfirmed PR remains on study awaiting a confirmatory scan. Tumor reduction was observed in six of eight evaluable patients.

In the Phase 1b trial, three confirmed PRs out of five evaluable patients were observed. Tumor reduction was observed in all five patients.

Overall, data in these 13 patients reflect an objective response rate (ORR) of 46% across the Phase 1b and Phase 2 patient populations, including confirmed and unconfirmed responses. Tumor reduction was observed in 11 of 13 patients.
The longest duration on study is more than 55 weeks and the patient remains on study.

In MET amplification patients treated with the SDD formulation, glesatinib also demonstrated clinical benefit:
In the Phase 2 trial, two unconfirmed PRs out of eight evaluable patients were observed. Neither of the unconfirmed responses remains on study. Tumor reduction was observed in six of eight evaluable patients.
The longest duration on study is more than 24 weeks and the patient remains on study.
The Company expects to provide an additional update on the glesatinib program in the second half of 2017.

Sitravatinib Program Update
Sitravatinib is being evaluated in a Phase 1b expansion trial designed to evaluate its safety and efficacy in multiple pre-specified cohorts of cancer patients with genetic mutations involving sitravatinib targets, including a cohort of NSCLC patients with RET fusion mutations.

As of a data cut-off of December 9, 2016, a total of six NSCLC patients with RET fusion mutations had been enrolled, four of whom were evaluable:
Of the four evaluable patients, one patient with a KIF5-B RET fusion demonstrated a confirmed PR and one patient with a DSP RET fusion has achieved an unconfirmed PR on initial scan, representing a 50% ORR, including confirmed and unconfirmed responses. Both patients remain on study. A third patient with RET fusion demonstrated tumor reduction of 29%, representing stable disease. Tumor reduction was observed in in all four patients.

The longest duration on study is more than 46 weeks and the patient remains on study.
The Phase 1b trial is also enrolling NSCLC patients with CBL mutations, CHR4q12 amplification, and AXL alterations. As of the data
cut-off date, no patients with these genetic mutations were evaluable.

Sitravatinib is also being evaluated in combination with nivolumab, a checkpoint inhibitor approved for the treatment of patients with a variety of solid tumors including NSCLC and metastatic renal cell carcinoma. Pre-clinical data indicate sitravatinib is an exceptionally potent inhibitor of the TAM (Tyro, Axl, Mer) and split (KDR, KIT) family tyrosine kinases which regulate multiple stages in the cancer immunity cycle and are thought to enhance anti-tumor immunity by improving the efficacy of checkpoint inhibitors (anti PD-1/PDL-1). The multicenter Phase 2 NSCLC trial enrolled its first patient in November 2016.
The Company expects to provide an additional update on the sitravatinib program in Q3 2017.

Mocetinostat Program Update
A Phase 1b/2 trial combining mocetinostat, an orally administered spectrum-selective Class 1 HDAC inhibitor, and durvalumab, MedImmune’s monoclonal antibody inhibiting PD-L1, continues to enroll patients with advanced solid tumors and NSCLC. The Company expects to provide an additional update on the mocetinostat program mid-year 2017.

Pre-Clinical Program Update
Two internally developed candidates are in pre-clinical development. The first is a highly-potent and potentially best-in-class LSD1 inhibitor with potential for rapid clinical proof-of-concept in small cell lung cancer or acute myeloid leukemia. An investigational new drug (IND) submission is planned for this compound in late 2017. Additionally, a mutant-selective KRAS inhibitor program is advancing to the candidate selection phase and prototype inhibitors have demonstrated marked tumor regression in KRAS mutant tumor models. An IND candidate selection is anticipated by the end of 2017.

About the glesatinib Phase 2 Trial ("AMETHYST")
AMETHYST is a multicenter, global Phase 2 trial designed to evaluate the safety and efficacy of glesatinib in NSCLC patients with MET genetic alterations who were previously treated with platinum-based chemotherapy and/or a checkpoint inhibitor.

AMETHYST pre-specified patient cohorts include NSCLC with MET Exon 14 deletion and MET amplification. Enrollment rates in the AMETHYST trial have been supported by the Company’s partnerships with molecular diagnostics companies providing commercially-available genetic testing, which have accelerated patient identification and enrollment.

MacroGenics’ MGD006 Granted Orphan Drug Status for AML by FDA

On January 5, 2016 MacroGenics, Inc. (Nasdaq: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to MGD006 (also known as S80880), a DART molecule that recognizes both CD123 and CD3, for the investigational treatment of acute myeloid leukemia (AML) (Press release, MacroGenics, JAN 5, 2017, View Source [SID1234517281]).

MGD006 is currently being evaluated in the U.S. and Europe in a Phase 1 dose-escalation study designed to assess the safety and tolerability of the molecule in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS). MacroGenics retains full development and commercialization rights to MGD006 in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development and has rights to MGD006 in all other countries.

The FDA orphan drug designation provides certain incentives for medications intended for the treatment, diagnosis or prevention of rare diseases. At present, these incentives include seven years of marketing exclusivity for the orphan indication, certain federal grants, tax credits and waiver of certain FDA fees.

"The FDA’s decision to grant orphan drug designation for MGD006 in AML is an important regulatory milestone for MacroGenics as we continue to develop this bispecific DART molecule in this difficult-to-treat disease," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "We believe MGD006 has the potential to be a significant advancement in the treatment of AML, and are pleased that the FDA has recognized the potential of MGD006 to benefit patients in need. We expect to select a dose this year to advance MGD006 into its next phase of clinical development."

About MGD006

MGD006 is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies including AML and MDS.

The primary mechanism of action of MGD006 is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

In December 2016, MacroGenics presented initial clinical experience from the ongoing Phase 1 study of MGD006. Dosing schema and supportive care regimens have been refined to enable therapeutic goals and decrease the effects of cytokine induction by MGD006, an anticipated event resulting from the engagement and activation of T lymphocytes. In addition, the Company continues to characterize the pharmacokinetic properties and clinical activity of MGD006 in AML patients.