On December 7, 2019 Aleta Biotherapeutics, a privately held immunotherapy company focused on transforming cellular therapeutics to allow a broad spectrum of cancer indications to be targeted, reported in vitro and in vivo results demonstrating that Aleta’s novel CD19-anti-CD20 bridging protein prevents and reverses CD19-negative relapse from CAR-CD19 T cell treatment (Press release, Aleta Biotherapeutics, DEC 7, 2019, View Source [SID1234552059]).

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"FDA-approved CAR-CD19 T cell therapies such as tisagenlecleucel and axicabtagene ciloleucel have demonstrated remarkable success in treating B cell cancers including refractory and relapsed acute lymphoblastic leukemia and non-Hodgkin lymphoma. However, relapse rates of up to 50% have been reported, most occurring within 6 months of CAR-CD19 T cell therapy. Some patients relapse due to the loss of expression of CD19 on tumor cells and other patients relapse because the cell therapy has failed to fully control tumor cell proliferation," said Paul Rennert, Ph.D., President and Chief Scientific Officer, Aleta Biotherapeutics. "The studies we presented today demonstrate that Aleta’s CD19-anti-CD20 bridging protein can reactivate CAR-CD19 T cells to prevent and to reverse relapses by redirecting CAR-CD19 T cells to the novel antigen CD20, present on the majority of B cell malignancy tumor cells. Aleta has identified a development candidate for the treatment of B cell malignancy patients relapsing from CAR-CD19 treatment and based on these and other studies, we are advancing this program into development and then into Phase 1 clinical trials."

Results Presented at ASH (Free ASH Whitepaper) 2019
A stabilized form of the CD19 extracellular domain (ECD) was cloned in frame with an anti-CD20 antibody fragment and an anti-albumin antibody fragment, to create a monomeric CD19-ECD-anti-CD20 bridging protein with extended circulating half-life characteristics. The protein was purified from a mammalian cell expression system. Protein stability, binding affinities, and cytotoxic activity were analyzed in vitro.

The Aleta CD19-anti-CD20 bridging protein was shown to be expressed at high levels, readily purified and highly stable. The purified bridging protein directed CAR19 cytotoxicity against CD19-negative/CD20-positive cells with superb potency (IC50 = 0.7 pM = 0.04 ng/ml). CAR-CD19 T cells that were previously activated by a CD19-positive tumor cell could subsequently be activated by a CD19-negative tumor cell in the presence of the Aleta CD19-anti-CD20 bridging protein.

In vitro, CAR19 T cells found and eliminated CD19-negative cells that escaped from CAR-CD19 T cell treatment. In vivo, CAR-CD19 T cells, plus the injected Aleta bridging protein, controlled tumor cell growth, preventing escape from therapy, while CAR-CD19 T cells alone did not prevent tumor relapse. The growth of an aggressive mantle-cell-derived tumor cell line was only delayed by therapy with CAR-CD19 T cells alone but was fully eradicated when CAR-CD19 cells were given along with Aleta’s CD19-anti-CD20 bridging protein injected systemically. In a parallel set of studies, it was shown that CAR-CD19 T cells modified to secrete the CD19-anti-CD20 bridging protein were as effective as CAR-CD19 T cells given in the presence of the purified bridging protein.

On December 6, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported preliminary tolerability and PK data from its ongoing Phase 1 dose-finding study of fimepinostat, a small molecule dual inhibitor of PI3K/HDAC and suppressor of MYC, in combination with venetoclax, a BCL-2 inhibitor, for the treatment of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including patients with double-hit/double-expressor (DH/DE) lymphoma (Press release, Curis, DEC 6, 2019, View Source [SID1234551998]).

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"We are very pleased with the progress in our ongoing Phase 1 study, with the combination of fimepinostat and venetoclax demonstrating a favorable tolerability profile thus far," said James Dentzer, President and Chief Executive Officer of Curis. "We believe demonstrating that this combination is generally well-tolerated for patients is a significant milestone, as both drugs have shown activity as monotherapies in this patient population and we believe activity will be improved by combining the two agents. Based on these data, we plan to initiate an expansion of the current study in 2020."

To date, the study has enrolled 11 patients, 6 patients in the first cohort and 5 patients in the second cohort. Patients in the first cohort received 30mg once-daily (QD) of fimepinostat and 400mg QD of venetoclax, while the patients in the second cohort received 60mg QD of fimepinostat and 400mg QD of venetoclax. To date the combination has been generally well-tolerated by patients.

"There is an urgent need for therapies targeting MYC and BCL-2 alterations, particularly in DH/DE lymphoma, a disease defined by these alterations and one of the deadliest types of lymphoma," said Robert Martell, M.D, Ph.D, Head of R&D at Curis. "We believe fimepinostat is unique in its ability to target MYC through simultaneous inhibition of both PI3K and HDAC. Venetoclax is a rapidly-acting inhibitor of BCL2, the other key abnormality in DH lymphoma. Supported by synergistic anti-cancer effects observed in preclinical models, we believe this is an ideal combination to target DLBCL and we look forward to gaining further insights on the combination from this study.

Dr. Martell continued: "The study was designed with initial patients undergoing a several-week run-in period allowing detailed PK interaction analysis and venetoclax ramp-up to be performed. In preliminary analyses, we found the combination to be generally well tolerated, with no dose-limiting toxicity (DLT) in the first cohort and one DLT of transient grade 3 diarrhea in the second cohort. Importantly, we found no drug-drug PK interaction that required dose modification of either agent. Drug-drug interactions are a major problem for many drugs combining with venetoclax, and we are encouraged that we have not seen such interaction to date with fimepinostat."

Curis’ ongoing Phase 1, open-label, multi-center, dose-finding 3+3 study is designed to evaluate the safety and tolerability, PK and pharmacodynamics, and preliminary activity of the fimepinostat and venetoclax combination in patients with DLBCL, including those with DH/DE lymphoma. Patients are enrolled in two cohorts in the study, with fimepinostat administered on a 5-days-on-2-days-off schedule in combination with venetoclax in 21-day cycles. Curis plans to initiate an expansion of the current study in 2020.

Conference Call Information

Curis management will host a conference call today, December 6, 2019, at 8:00 a.m. ET, to discuss these results. To access the live conference call, please dial 1-888-346-6389 from the United States or 1-412-317-5252 from other locations, shortly before 8:00 a.m. ET. The conference call can also be accessed on the Curis website at www.curis.com in the Investors section.

On December 6, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported updated preliminary data from its ongoing Phase 1 dose escalation study of CA-4948, an IRAK4 kinase inhibitor, for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin’s lymphoma (NHL), including patients with diffuse large B-cell lymphoma (DLBCL), Waldenström’s macroglobulinemia (WM) and oncogenic MYD88 mutations (Press release, Curis, DEC 6, 2019, View Source [SID1234551999]).

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"We are very encouraged by the anti-cancer activity that we have observed to date from CA-4948 during dose escalation in our Phase 1 study," said Robert Martell, MD, PhD, Head of R&D at Curis. "Notably, five of the six patients evaluable for anti-cancer activity at the two highest dose levels of CA-4948 have experienced reduced tumor burden. Additionally, treatment for three of these five patients is ongoing after 33 to 51 weeks. These findings illustrate dose dependent activity compared to earlier dose levels."

Dr. Martell continued: "We believe these results achieve the desired activity outcome for a targeted single agent treating malignancies with complex molecular genetics. Unlike the minority of cancers with a single driver mutation, these genetically complex malignancies have aberrant signaling through multiple signaling pathways. One such pathway is the oncogenic TLR pathway, which depends on IRAK4. Such complex cancers represent the bulk of actual medical need in oncology today, and we believe the most effective therapeutic approaches in these situations is to target multiple such mechanisms. Indeed, synergy was observed preclinically when combining CA-4948 with either BTK inhibitors or a BCL2 inhibitor, and we intend to explore combinations in the clinic."

"We believe these updated clinical data further support the potential of CA-4948 to become a safe, effective therapeutic option for patients with NHL," said James Dentzer, President and Chief Executive Officer of Curis. "CA-4948 is currently the most advanced molecule targeting IRAK4 in clinical development for cancer and given these exciting results, we intend to move aggressively to advance CA-4948 with the goal of bringing this promising new therapy to patients in need. We look forward to expanding the development of CA-4948 with two new clinical trials in 2020 that will study CA-4948 in AML/MDS and in combination therapy in NHL."

The reported data are from Curis’s ongoing Phase 1, open-label, dose escalation 3+3 study designed to evaluate the safety and tolerability of CA-4948, in addition to pharmacokinetics, pharmacodynamics, and anti-cancer activity, in patients with R/R NHL. Patients have been treated in continuous 21-day cycles and at dose levels of 50mg once-daily (QD), 50mg twice-daily (BID), 100mg QD, 100mg BID, 200mg BID and 400mg BID.

Key findings include:

CA-4948 was demonstrated to be generally well-tolerated.
Patients enrolled to date include patients with tumor types of DLBCL, WM, marginal zone lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma.
Anti-cancer activity, as measured by the reduction of tumor burden, was observed in:
5 out of 6 evaluable patients in the highest dose cohorts of 200mg BID and 400mg BID, with a mean reduction of 29% (ranging from 5% to 47%).
One patient with WM, who dose escalated from 50mg BID to 100mg BID, and then to 200mg BID, experienced dose-corresponding reductions in tumor burden. This patient remains on therapy.
One patient with DLBCL enrolled in the 200mg dose cohort remains on study and has seen tumor reductions of 35%.
One patient treated at 100mg QD had a dose-limiting toxicity (DLT) of maculo-papular rash, which was resolved after steroid treatment. Another patient treated at 400mg BID experienced a DLT of Grade 3 rhabdomyolysis.
Curis is currently evaluating patients at the 400mg BID dose of CA-4948 in its Phase 1 study and plans to continue dose escalation until the maximum tolerated dose and or recommended Phase 2 dose of CA-4948 is determined.

Conference Call Information

Curis management will host a conference call today, December 6, 2019, at 8:00 a.m. ET, to discuss these results. To access the live conference call, please dial 1-888-346-6389 from the United States or 1-412-317-5252 from other locations, shortly before 8:00 a.m. ET. The conference call can also be accessed on the Curis website at www.curis.com in the Investors section.

On December 6, 2019 IVERIC bio, Inc. (Nasdaq: ISEE) (the "Company"), reported the pricing of an underwritten public offering of 6,250,000 shares of its common stock at a price to the public of $4.000 per share and, to certain investors in lieu of common stock, pre-funded warrants to purchase 3,750,000 shares of its common stock at a price to the public of $3.999 per pre-funded warrant, in each case less underwriting discounts and commissions (Press release, Ophthotech, DEC 6, 2019, View Source [SID1234552193]). The purchase price of each pre-funded warrant represents the per share public offering price for the common stock, minus the $0.001 per share exercise price of such pre-funded warrant. The aggregate gross proceeds from the offering are expected to be approximately $40.0 million before underwriting discounts and commissions and offering expenses payable by the Company. In addition, in connection with the offering, the Company has granted the underwriters an option for a period of 30 days to purchase up to an additional 1,500,000 shares of common stock at the public offering price, less underwriting discounts and commissions. All of the securities are being offered by the Company.

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Cowen is acting as the sole book-running manager for the offering. Wedbush Securities is acting as the lead manager for the offering. The offering is expected to close on or about December 10, 2019, subject to customary closing conditions.

A shelf registration statement on Form S-3 (File No. 333-226497) relating to the shares of common stock offered in the public offering was filed with the Securities and Exchange Commission (the "SEC") and was declared effective on August 15, 2018. The offering is being made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A final prospectus supplement related to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained, when available, by contacting: Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by email at [email protected], or by telephone at (833) 297-2926 or Wedbush Securities Inc., Two Embarcadero Center, Suite 600, San Francisco, CA 94111, Attn: ECM Prospectus Department, by email at [email protected], or by telephone at (415) 274-7800.

This press release does not constitute an offer to sell, or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 6, 2019 IntelGenx Technologies Corp. (TSXV: IGX) (OTCQX: IGXT) (the "Company" or "IntelGenx") reported that it intends to issue 415,178 common shares of the Corporation (the "Common Shares") at a deemed price of CAD $0.73 per Common Share in payment of an aggregate of $303,080 in interest owing on the Corporation’s 8.00% convertible unsecured subordinated debentures due June 30, 2020 (the "Debentures") (Press release, IntelGenx, DEC 6, 2019, View Source [SID1234552000]).

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Under the terms of the trust indenture governing the Debentures (the "Indenture"), the Corporation has the option to pay the semi-annual interest on the Debentures in either cash or Common Shares, subject to customary conditions set forth in the Indenture. The issuance of the Common Shares in payment of interest on the Debentures is subject to the acceptance by the TSX Venture Exchange Inc. The Common Shares issued in payment of interest on the Debentures will be issued pursuant to exemptions from the prospectus requirements of applicable securities laws.