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Mirati Presents Data From Ongoing Phase 2 Clinical Trial Of Mocetinostat In Combination With Durvalumab At The SITC 33rd Annual Meeting

On November 9, 2018 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported data from the ongoing Phase 2 clinical trial of mocetinostat in combination with durvalumab (IMFINZI) in non-small cell lung cancer (NSCLC) patients at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington, D.C (Press release, Mirati, NOV 9, 2018, View Source [SID1234531095]). The data will be presented today in a poster and also in an oral presentation on Sunday, November 11th.

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Highlights from the Oral Presentation

The clinical trial is a Phase 2 study evaluating the efficacy and safety of mocetinostat in combination with durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with an immune checkpoint inhibitor. As of the data cut-off date of October 2, 2018:

29 patients were evaluable for response with at least one radiographic scan. Patients had a median of two lines of previous therapy.
12/29 evaluable patients demonstrated tumor reductions.
6/29 evaluable patients demonstrated tumor reductions of greater than 30%.
5/29 evaluable patients achieved a confirmed Partial Response (PR).
4/29 evaluable patients, including 2 responding patients, remained on treatment at the time of data cut-off.
A preliminary Kaplan-Meier estimate of median duration of response was greater than 5 months.
The combination has been well-tolerated and most adverse events (AEs) were grade 1 or 2.
"The combination of mocetinostat with durvalumab demonstrated clinical benefit in this difficult to treat population of checkpoint inhibitor refractory NSCLC patients," said Charles Baum, M.D., Ph.D., President and Chief Executive Officer at Mirati Therapeutics. "While these results are promising, we have made the strategic portfolio decision to prioritize sitravatinib for further development in the treatment of checkpoint inhibitor refractory patients and plan to explore collaborative opportunities to further develop mocetinostat."

The Company recently announced plans to initiate a Phase 3 clinical trial comparing sitravatinib in combination with checkpoint inhibitor therapy to docetaxel in second line checkpoint inhibitor refractory NSCLC patients in the first half of 2019. In addition, the Company also announced plans to initiate a Phase 1/2 clinical trial of MRTX849, an oral inhibitor of KRAS G12C, in patients with NSCLC, colorectal cancer, and other solid tumors that harbor the G12C mutation. Trial initiation is planned for early 2019 after the investigational new drug (IND) allowance letter is received from the U.S. Food and Drug Administration (FDA) for the application that was filed in October 2018.

About Mocetinostat

Mocetinostat is an oral, Class I and IV selective histone deacetylase (HDAC) inhibitor. Inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. Mocetinostat is being evaluated in a Phase 2 clinical trial in combination with durvalumab (IMFINZI) in non-small cell lung cancer (NSCLC) patients who have experienced disease progression following prior treatment with a checkpoint inhibitor.

About Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion clinical trial emphasizing enrollment of patients whose tumors harbor specific mutations in the CBL protein. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma. Sitravatinib potently inhibits these RTKs and is being investigated as a treatment option for cancer patients with CBL mutations.

About MRTX849

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated broad-spectrum tumor regression in a large cohort of KRAS G12C positive, pre-clinical in-vivo human tumor models. MRTX849 demonstrated complete regression of tumors in a subset of models at well-tolerated dose levels. Early proof-of-concept clinical data is anticipated in 2019.

Celldex Presents Promising Interim Data from Phase 1 Study of Differentiated CD40 Agonist CDX-1140 at the Society for Immunotherapy of Cancer’s 33rd Annual Meeting

On November 9, 2018 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported interim data Phase 1 dose-escalation study of CDX-1140, a fully human agonist anti-CD40 antibody (Press release, Celldex Therapeutics, NOV 9, 2018, View Source [SID1234531094]). CD40, expressed on dendritic cells and other antigen presenting cells, has long been an important target for immunotherapy, as it plays a critical role in the activation of innate and adaptive immune responses. The data were presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting.

"CDX-1140 was specifically designed to balance systemic dosing and safety, which has proven elusive for CD40-targeted activating therapeutics," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "We have completed four of the potential eight monotherapy dose levels and, to date, CDX-1140 has been well tolerated. Importantly, we are observing dose-dependent biological effects consistent with CD40-mediated immune cell activity. Based on these positive findings, we have expanded development of the program and recently initiated a combination cohort with CDX-301, our dendritic cell growth factor, to increase the number of dendritic cells which are critical to initiating antitumor immunity and a key target for CDX-1140. We also expanded the study to include patients with non-Hodgkin’s lymphoma as our preclinical work has demonstrated that CDX-1140 has direct killing effect on CD40-expressing NHL cells. We look forward to continued data updates from this study in the first half of 2019."

Potent CD40 agonist antibodies have shown encouraging results in early clinical studies; however, systemic toxicity associated with broad CD40 activation has limited their dosing. CDX-1140 has unique properties relative to other CD40 agonist antibodies: potent agonist activity resulting in dendritic cell and B cell activation is independent of Fc receptor interaction, contributing to more consistent, controlled immune activation; CD40 ligand (CD154) binding is not blocked, allowing potential synergistic, antigen-specific agonist activity; and the antibody promotes strong immune activation without significant adverse events in preclinical toxicology studies.

Study Highlights:
Seventeen patients with solid tumors were enrolled at the time of data analysis (n=13 monotherapy; n=4 combination). Four single-agent dosing cohorts have completed (0.01; 0.03, 0.09 and 0.18 mg/kg) and enrollment to the 0.36 mg/kg monotherapy cohort is ongoing. Enrollment to the first CDX-1140/CDX-301 combination cohort is ongoing (0.09 mg/kg and 75 ug/kg, respectively). Dose dependent biological effects consistent with CD40-mediated immune activation have been observed in the study and no maximum tolerated dose (MTD) has been identified to date. Continued enrollment is ongoing to define the MTD and select a dose for disease-specific expansion cohorts that will be monitored for clinical activity.

CDX-1140 has been well tolerated to date. One patient experienced a grade 3 dose-limiting toxicity (DLT) (pneumonitis and hypoxia) at the single-agent 0.18 mg/kg dose. Per protocol, three additional patients were enrolled in the cohort and no additional DLTs have been observed in this or subsequent cohorts.

There have been no significant drug-related changes observed to date in liver function tests or platelets, which have been observed with other CD40 agonists.

Transient dose-dependent pharmacodynamic effects have been observed including activation of immune cells and increases in pro-inflammatory cytokines and chemokines in the blood, which are consistent with CD40-mediated immune activation and the hypothesis that CDX-1140 may achieve dose levels optimal for systemic exposure.
A combination cohort with Celldex’s dendritic cell growth factor CDX-301 has been added to the CDX-1140 study. Dendritic cells, which express CD40, are rarely present or completely absent within the tumor microenvironment and are critical for initiating anti-tumor immunity. CDX-301 is being utilized to increase the number of dendritic cells in blood and tissue available for CDX-1140 activation. CDX-1140 should, in turn, activate the dendritic cells, an important step for enhancing anti-tumor immune responses. While this combination cohort just recently opened to enrollment, preliminary evidence of enhanced immune activation has been observed. Patients continue to be monitored for toxicity with no DLT observed to date.
The study has also been amended to allow for the inclusion of patients with CD40-expressing B cell lymphomas (subtypes of non-Hodgkin lymphoma or NHL) in up to two single-agent cohorts. Both immune activation and direct killing of CD40-expressing NHL cells by CDX-1140 have been shown to contribute to antitumor activity. Several B cell lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, also express both CD40 and CD27. Celldex’s varlilumab is a potent CD27 agonist and has been shown to synergize with CDX-1140 in NHL models and may be evaluated in combination with CDX-1140 in the future.
About CDX-1140
CDX-1140 is a fully human antibody targeted to CD40, a key activator of immune response that is found on dendritic cells, macrophages and B cells and is also expressed on many cancer cells. Potent CD40 agonist antibodies have shown encouraging results in early clinical studies; however, systemic toxicity associated with broad CD40 activation has limited their dosing. CDX-1140 has unique properties relative to other CD40 agonist antibodies: potent agonist activity resulting in dendritic cell and B cell activation is independent of Fc receptor interaction, contributing to more consistent, controlled immune activation; CD40 ligand (CD154) binding is not blocked, allowing potential synergistic, antigen-specific agonist activity; and the antibody promotes strong immune activation without significant adverse events in preclinical toxicology studies. CDX-1140 has also shown direct antitumor activity in preclinical lymphoma models. Celldex believes that the potential for CDX-1140 will be best defined in combination studies with other immunotherapies, including CDX-301, Celldex’s dendritic cell growth factor, varlilumab, Celldex’s potent CD27 agonist, checkpoint blockade, radiation and other conventional cancer treatments.

Immune Design to Present at Jefferies 2018 London Healthcare Conference

On November 9, 2018 Immune Design (Nasdaq: IMDZ), an immunotherapy company focused on next-generation therapies in oncology, reported that Carlos Paya, M.D., Ph.D., President and Chief Executive Officer, will present at the Jefferies 2018 London Healthcare Conference on Wednesday, November 14, 2018 at 9:40 a.m. GMT / 4:40 a.m. ET (Press release, Immune Design, NOV 9, 2018, View Source [SID1234531093]).

A live webcast of the presentation will be available online from the investor relations page of the company’s corporate website at View Source After the live webcast, an archive of the presentation will be available on the company website for 30 days.

Aurinia to Participate in November Investor Conferences

On November 9, 2018 Aurinia Pharmaceuticals Inc., (NASDAQ:AUPH)(TSX:AUP) reported its Chairman and CEO, Richard Glickman, will participate in two upcoming investor conferences (Press release, Aurinia Pharmaceuticals, NOV 9, 2018, View Source [SID1234531092]).

Wednesday, November 14, 2018, Aurinia will present a company overview at the Jefferies 2018 London Healthcare Conference in London, UK at 10:00am GMT. The presentation will be webcast live and can be accessed via the investor section of the Aurinia website, www.auriniapharma.com. A replay of will also be archived on the site following the event.

Tuesday, November 27, 2018, Aurinia will participate in One-on-One Meetings at the Evercore ISI HealthCONx Conference in Boston, MA.

Omeros Announces Pricing of $210 Million Offering of Convertible Senior Notes Due 2023

On November 9, 2018 Omeros Corporation (Nasdaq: OMER) ("Omeros") reported the pricing of an offering of $210 million aggregate principal amount of its 6.25% Convertible Senior Notes due 2023 (the "Notes") in a private offering (the "Offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933 (the "Securities Act") (Press release, Omeros, NOV 9, 2018, View Source;p=irol-newsArticle_Print&ID=2376484 [SID1234531091]). Omeros has granted the initial purchasers of the Notes an option to purchase up to an additional $40 million aggregate principal amount of the Notes on the same terms and conditions referenced above.

The Notes will be senior unsecured obligations of Omeros and interest will be payable semi-annually in arrears at a rate of 6.25% per annum. The Notes will mature on November 15, 2023, unless converted, repurchased or redeemed in accordance with their terms prior to such date. The Notes will be convertible, upon the satisfaction of certain conditions or during specified periods, into cash, shares of Omeros’ common stock or a combination thereof as Omeros elects at its sole discretion. Omeros will have the right to redeem the Notes on or after November 15, 2019, subject to certain conditions.

The initial conversion rate of the Notes is 52.0183 shares of Omeros’ common stock per $1,000 principal amount of the Notes, which is equivalent to an initial conversion price of approximately $19.22 per share of Omeros’ common stock, and is subject to adjustment in certain circumstances. This initial conversion price represents a premium of approximately 20% over the last reported sale price on November 8, 2018 of Omeros’ common stock of $16.02 per share. Omeros has entered into the capped call transaction described below in order to avoid dilution to Omeros’ shareholders from conversions of the Notes if Omeros’ common stock price does not exceed $28.8360, which represents a premium of 80% over the last reported sale price of Omeros’ common stock.

The aggregate gross proceeds to Omeros from the offering of the Notes will be $210 million, exclusive of any proceeds attributable to the initial purchasers’ possible exercise of their option to purchase additional Notes. Omeros intends to use a portion of the net proceeds of the offering to repay in full the amounts outstanding under Omeros’ secured Term Loan Agreement with CRG Servicing LLC (the "Term Loan Agreement"), which has an annual interest rate of 12.25% and matures on September 30, 2022. Amounts repaid will include all accrued but unpaid interest and prepayment fees under the Term Loan Agreement.

Cantor Fitzgerald & Co. and UBS Investment Bank are acting as joint bookrunners for the offering. Cantor Fitzgerald & Co. is also acting as the sole structuring advisor for the offering.

In connection with the pricing of the Notes, Omeros entered into a capped call transaction with Royal Bank of Canada, or RBC. The capped call transaction is intended to minimize the potential dilution of Omeros’ common stock and/or offset potential cash payments in excess of the principal amount of the converted Notes upon conversion of the Notes, as Omeros elects at its sole discretion, in the event that the market price per share of Omeros’ common stock, as measured under the terms of the capped call transaction, is greater than the strike price of the capped call transaction, which initially corresponds to the conversion price of the Notes and is subject to anti-dilution adjustments substantially similar to those applicable to the conversion rate of the Notes. If, however, the market price per share of Omeros’ common stock, as measured under the terms of the capped call transaction, exceeds the cap price of the capped call transaction, there would nevertheless, upon conversion, be dilution or a cash expenditure, as elected by Omeros in its sole discretion, to the extent that such market price exceeds the cap price of the capped call transaction. The cap price under the capped call transaction will initially be $28.8360 per share, which represents a premium of 80% over the last reported sale price of Omeros’ common stock on November 8, 2018, and is subject to certain adjustments under the terms of the capped call transaction. If the initial purchasers exercise their option to purchase additional Notes, Omeros expects to enter into an additional capped call transaction.

Omeros has been advised that, in connection with establishing its initial hedge of the capped call transaction, RBC and/or its affiliates expect to enter into various derivative transactions with respect to Omeros’ common stock concurrently with or shortly after the pricing of the Notes. This activity could increase (or reduce the size of any decrease in) the market price of Omeros’ common stock or the Notes at that time. In addition, Omeros has been advised that RBC and/or its affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Omeros’ common stock and/or purchasing or selling Omeros’ common stock in secondary market transactions following the pricing of the Notes and prior to the maturity of the Notes (and are likely to do so during any observation period related to a conversion of Notes). This activity could also cause or avoid an increase or a decrease in the market price of Omeros’ common stock or the Notes.

In addition to repaying the Term Loan Agreement and entering into the capped call transaction, Omeros intends to use the remainder of the net proceeds of the offering for general corporate purposes, including funding research and development for Omeros’ OMS721 programs and clinical trials, pre-clinical studies, manufacturing and other costs associated with advancing Omeros’ product candidates toward Marketing Authorization Application, Biologics License Application and New Drug Application submissions. If the initial purchasers exercise their option to purchase additional notes, then Omeros intends to use the additional net proceeds to fund the cost of entering into any additional capped call transactions and for general corporate purposes as described above. The offering is expected to close on November 15, 2018, subject to customary closing conditions.

This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities of Omeros. Any offers of the Notes will be made only by means of a private offering memorandum. The offer and sale of the Notes and any shares of Omeros common stock issuable upon conversion of the Notes have not been, and will not be, registered under the Securities Act or the securities laws of any other jurisdiction, and the Notes and such shares may not be offered or sold in the United States absent registration or an applicable exemption from the Securities Act and applicable state laws.