On November 5, 2019 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology, reported positive preclinical results further elucidating the mechanism of action of BL-8040 in combination with an anti PD-1 and chemotherapy (Press release, BioLineRx, NOV 5, 2019, View Source [SID1234550288]). The results, summarized in a poster entitled, "Combination of BL-8040, anti PD-1 and chemotherapy significantly reduced pancreatic tumor growth and changed the balance between CD4+/FOXP3+ cells and CD8+ cells in the tumor," will be presented on November 8, 2019 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Maryland.

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"The results seen in this preclinical pancreatic cancer study support our hypothesis that the triple combination of BL-8040, anti-PD-1 and chemotherapy helps combat this difficult to treat cancer," said Philip Serlin, Chief Executive Officer of BioLineRx. "These preclinical data from the triple combination study support the mechanism of action of BL-8040 demonstrated in earlier clinical data from the dual combination of BL-8040 and pembrolizumab, showing a reduction in immuno-suppressive cells, accompanied by an increase in activated effector CD8+ T cells. We believe the ability of BL-8040 to modulate the tumor microenvironment allows for better activation of immune effector cells when combined with chemotherapy and immunotherapy. We are very hopeful that this anti-tumor activity will be confirmed in humans as we eagerly await results from the triple combination arm of our COMBAT/KEYNOTE-202 Phase 2 study of BL-8040, KEYTRUDA and chemotherapy in metastatic pancreatic cancer, which we expect to report by year end."

About the Pre-Clinical Study
The pre-clinical study assessed the effects of BL-8040, anti-PD-1 and chemotherapy (Irinotecan, Fluorouracil and Leucovorin), both alone and in various combinations, on tumor growth and immune cell constitution in a mouse model for pancreatic cancer.

Key findings include:

•The triple combination of BL-8040+anti-PD-1+chemotherapy had a significantly better effect on tumor growth compared to chemotherapy alone or any dual combination with chemotherapy.

The triple combination of BL-8040+anti-PD-1+chemotherapy showed the best effect in modulation of the tumor microenvironment, resulting in reduction in immunosuppressive cells, and accompanied by increase of activated T effector cells.

About BL-8040
BL-8040 is a short synthetic peptide that functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor over-expressed in many human cancers. CXCR4 has been shown to be correlated with poor prognosis, and plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance. CXCR4 is also directly involved in the homing and retention of hematopoietic stem cells (HSCs) and various hematological malignant cells in the bone marrow.

In a number of clinical and preclinical studies, BL-8040 has shown a critical role in immune cell trafficking, tumor infiltration by immune effector T cells and reduction in immunosuppressive cells within the tumor niche, turning "cold" tumors, such as pancreatic cancer, into "hot" tumors (i.e., sensitizing them to immune check point inhibitors). BL-8040-mediated inhibition of the CXCR4-CXCL12 (SDF-1) axis has also shown robust mobilization of HSCs for transplantation in hematological malignancies.

BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On November 5, 2019 Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) reported financial results for the quarter and nine months ended September 30, 2019 (Press release, Conatus Pharmaceuticals, NOV 5, 2019, View Source [SID1234550316]).

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Recent Developments

In June 2019, Conatus announced that top-line results from its ENCORE-LF clinical trial of emricasan did not meet its primary endpoint, and, Conatus and its partner, Novartis, had no further development plans for emricasan. In September 2019, Conatus and Novartis mutually agreed to terminate the collaboration agreement between the parties for the global development and commercialization of emricasan.

As previously announced, Conatus has engaged Oppenheimer & Co., Inc., as its financial advisor to assist in the exploration and evaluation of strategic alternatives to enhance shareholder value. There can be no assurance of a successful outcome from these efforts, or of the form or timing of any such outcome.

In connection with the discontinuation of emricasan and Conatus’ efforts to explore and evaluate strategic alternatives, Conatus announced in June 2019 that it was implementing a restructuring plan in order to extend its resources, which included reducing staff and suspending development of its inflammasome disease candidate, CTS-2090, and in September 2019 it implemented another restructuring plan in order to extend its resources, which included further reducing staff.

Financial Results
The net loss for the third quarter of 2019 was $3.3 million compared with $4.6 million for the third quarter of 2018. The net loss for the first nine months of 2019 was $8.7 million compared with $14.1 million for the first nine months of 2018.

All revenues were related to the company’s collaboration with Novartis. Total revenues were $3.4 million for the third quarter of 2019 compared with $7.7 million for the third quarter of 2018. Total revenues were $21.2 million for the first nine months of 2019 compared with $26.2 million for the first nine months of 2018. The decreases in revenues for both periods were primarily due to lower emricasan-related research and development expenses resulting in corresponding lower revenues from Novartis.

Research and development expenses were $4.7 million for the third quarter of 2019 compared with $9.7 million for the third quarter of 2018. The decrease in research and development expenses was primarily due to lower spending related to emricasan-related activities. Research and development expenses were $22.7 million for the first nine months of 2019 compared with $32.5 million for the first nine months of 2018. These decreases were primarily due to lower emricasan-related research and development expenses.

General and administrative expenses were $2.0 million for the third quarter of 2019 compared with $2.7 million for the third quarter of 2018. General and administrative expenses were $7.7 million for the first nine months of 2019 compared with $8.0 million for the first nine months of 2018. These decreases were primarily due to lower personnel costs resulting from the restructuring plan announced in June 2019.

Cash, cash equivalents and marketable securities were $22.7 million at September 30, 2019, compared with $40.7 million at December 31, 2018. The company is projecting a year-end 2019 net balance of cash, cash equivalents and marketable securities of between $10 million and $15 million.

On November 5, 2019 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, reported that it will report its third quarter 2019 financial and operating results on Tuesday, November 12, 2019, following the close of the U.S. financial markets (Press release, Lineage Cell Therapeutics, NOV 5, 2019, View Source [SID1234550332]). Lineage management will also host a conference call and webcast on Tuesday, November 12, 2019, at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss its third quarter 2019 financial results and to provide a business update.

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Interested parties may access the conference call by dialing (866) 888-8633 from the U.S. and Canada and (636) 812-6629 from elsewhere outside the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through November 19, 2019, by dialing (855) 859-2056 from the U.S. and Canada and (404) 537-3406 from elsewhere outside the U.S. and Canada and entering conference ID number 1473397.

On November 5, 2019 Vericel Corporation (NASDAQ:VCEL), a leader in advanced therapies for the sports medicine and severe burn care markets, reported financial results for the third quarter ended September 30, 2019, and recent business highlights (Press release, Vericel, NOV 5, 2019, View Source [SID1234550348]).

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Third Quarter 2019 Financial Highlights

Total net product revenues increased 36% to $30.5 million compared to $22.5 million in the third quarter of 2018, marking the tenth consecutive quarter with record revenues for the reported quarter;

MACI net revenue of $20.6 million and Epicel net product revenue of $9.9 million, the highest quarterly Epicel revenue in history;

Gross margin of 69% compared to gross margin of 64% in the third quarter of 2018;

Net income of $3.5 million, or $0.07 per share, compared to a net loss of $1.1 million, or $0.02 per share, in the third quarter of 2018;

Non-GAAP adjusted EBITDA of $6.8 million compared to $0.9 million in the third quarter of 2018;

Operating cash flow of $7.9 million;

As of September 30, 2019, the company had $74.7 million in cash and short-term investments compared to $82.9 million as of December 31, 2018; and

Full year 2019 revenue guidance for MACI and Epicel raised to $116 to $118 million compared to previous full year revenue guidance of $112 to $116 million.

Recent Business Highlights

During and since the third quarter of 2019, the company:

Announced plans to expand the MACI sales force from 49 to 76 sales representatives and from six to nine sales regions by the second quarter of 2020;

Completed an initial expansion of the burn care sales team from six to nine sales representatives and burn clinical specialists; and

Announced initiation of the NexoBrid Expanded Access Treatment Protocol (NEXT) to treat patients with deep partial- and full-thickness burns in the United

States during the preparation and review of the NexoBrid Biologics License Application.

"We are very pleased with the growth of our business and expect to maintain strong double-digit revenue growth for the foreseeable future as we continue to make targeted investments in our sports medicine and burn care commercial franchises," said Nick Colangelo, president and CEO of Vericel. "Given the consistent improvement in our gross profit and operating margin, we believe that we are also well-positioned to generate strong profit and cash flow growth in the years ahead."

Third Quarter 2019 Results
Total net product revenues for the quarter ended September 30, 2019 increased 36% to $30.5 million compared to $22.5 million in the third quarter of 2018. Total net product revenues for the quarter included $20.6 million of MACI (autologous cultured chondrocytes on porcine collagen membrane) net revenue and $9.9 million of Epicel (cultured epidermal autografts) net revenue, compared to $16.4 million of MACI net revenue and $6.0 million of Epicel net revenue, respectively, in the third quarter of 2018.

Gross profit for the quarter ended September 30, 2019 was $21.2 million, or 69% of net revenues, compared to $14.3 million, or 64% of net revenues, for the third quarter of 2018.

Total operating expenses for the quarter ended September 30, 2019 were $18.1 million, compared to $15.7 million for the same period in 2018. The increase in operating expenses was primarily due to a $1.1 million increase in stock-based compensation expenses, a $0.8 million increase in marketing expenses and a $0.7 million increase in MACI sales force expenses driven by the sales force expansion in the second quarter of 2019.

Vericel’s net income for the quarter ended September 30, 2019 was $3.5 million, or $0.07 per share, compared to a net loss of $1.1 million, or $0.02 per share, for the third quarter of 2018.
Non-GAAP adjusted EBITDA was $6.8 million for the quarter ended September 30, 2019 compared to $0.9 million in the third quarter of 2018. A table reconciling non-GAAP measures is included in this press release for reference.

As of September 30, 2019, the company had $74.7 million in cash and short-term investments compared to $82.9 million as of December 31, 2018.

Full Year 2019 Financial Guidance
The company now expects total MACI and Epicel net product revenues for the full year 2019 to be in the range of $116 to $118 million, compared to the previous full year revenue guidance of $112 to $116 million.

Conference Call Information
Today’s conference call will be available live at 8:30am Eastern Standard Time and can be accessed through the Investor Relations section of the Vericel website at http://

investors.vcel.com/events-presentations. A slide presentation with highlights from today’s conference call will be available on the webcast and in the Investor Relations section of the Vericel website. Please access the site at least 15 minutes prior to the scheduled start time in order to download the required audio software if necessary. To participate in the live call by telephone, please call (877) 312-5881 and reference Vericel Corporation’s second-quarter 2019 investor conference call. If calling from outside the U.S., please use the international phone number (253) 237-1173.

If you are unable to participate in the live call, the webcast will be available at View Source until November 5, 2020. A replay of the call will also be available until 11:00am (EDT) on November 10, 2019 by calling (855) 859-2056, or from outside the U.S. at (404) 537-3406. The conference ID is 1685887.

On November 5, 2019 Senti Biosciences, the gene circuit company focused on outsmarting complex diseases with intelligent medicines, reported that Senti scientists will present data at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held November 6-10, 2019, in National Harbor, Maryland (Press release, Senti Biosciences, NOV 5, 2019, View Source [SID1234550364]).

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Senti’s gene circuit platform enables the programming of any cell and gene therapy modality, including immune cells, stem cells, and viral vectors. The poster presentation highlights preclinical data from one of Senti’s programs, SENTI-101, an allogeneic cell therapy designed to treat patients with ovarian cancer and other solid tumors.

"This SITC (Free SITC Whitepaper) poster presentation is an important milestone for Senti Biosciences because it reveals an exciting translational application of our gene circuit platform, which has the potential to broadly transform cell and gene therapies," said Dr. Timothy Lu, CEO of Senti Biosciences.

The SENTI-101 program uses tumor-homing allogeneic cells as a drug delivery vehicle to achieve localized, combinatorial expression of two cytokines. This pair of cytokines activates a multifactorial immune response against solid tumors, and turns immunologically cold tumors hot. SENTI-101 was developed through Senti’s systematic design-build-test-learn process, wherein more than 250 different gene circuits including individual, two-wise and three-wise combinations of immune effectors were tested for their ability to treat cold tumors and trigger a robust tumor immunity cycle. This approach of programming artificial pharmacology into allogeneic cells enables delivery of high concentrations of multi-factorial immunotherapies locally in the tumor microenvironment, which Senti believes will be critical to transforming therapy for solid tumors.

"There’s a huge unmet need when it comes to developing treatments for patients whose tumors do not respond to checkpoint inhibitors, and we are excited about the potential for SENTI-101 to help these patients," said Gary Lee, Ph.D., Chief Scientific Officer at Senti Biosciences.

SENTI-101 is a novel product candidate comprising allogeneic mesenchymal stromal cells (MSCs) genetically modified to express a combination of immunomodulatory cytokines — Interleukin 12 (IL-12) and Interleukin 21 (IL-21). Together, IL-12 and IL-21 enable highly effective and complementary stimulation of anti-tumor immunity.

Upon administration in preclinical models, SENTI-101:

Innately homes to peritoneal tumors (>10-fold higher vs. normal tissues, p≤0.0001)
Secretes IL-12 and IL-21 in a localized and sustained fashion within tumors of the peritoneal space (~100-fold greater in peritoneal space vs. serum [p≤0.002])
Induces a robust and durable anti-tumor immune response, resulting in more than 200-fold (p≤0.0001) and 10-fold (p≤0.0001) reduction in tumor burden in CT26-fLUC and B16-F10-fLUC models, respectively
Prolongs tumor-free survival compared to controls and checkpoint inhibitor therapy in syngeneic tumor models, including the checkpoint refractory B16-F10 model, and notably, mice treated with the SENTI-101 combination outperformed those treated with MSCs expressing each individual cytokine
Additionally, surviving mice rejected a second round of newly implanted tumor cells, thereby demonstrating anti-tumor immune memory
Mechanistically involves multiple important immune cell subtypes, including CD4 and CD8 T cells, antigen-presenting cells (APCs), B cells and NK cells
The SITC (Free SITC Whitepaper) abstract can be accessed here: http://bit.ly/2Wt2wli

Recent Corporate Update

In addition to its gene circuits and translational biology capabilities, Senti has established in-house process development, regulatory, and clinical expertise to pursue IND-enabling studies, GMP manufacturing, and clinical protocol development for its pipeline. Additional gene circuit cell therapy programs for solid tumors and difficult-to-treat liquid tumors are also underway, with plans to advance candidates for clinical development in the next year.

Senti’s corporate strategy is focused on internal product development, as well as establishing collaborations with other companies. The gene circuit platform can be paired with a variety of complementary technologies to create next-generation cell and gene therapies with improved performance. For example, Senti’s engineered promoters and logic gates enable cell and gene therapies with programmable specificity and high activity in defined cell states or cell types. In addition, Senti’s Pro-Dial platform allows for cell and gene therapies to be titrated up or down in a rheostat fashion with FDA-approved small molecule drugs. These technologies have the potential to make cell and gene therapies controllable, targeted and dynamic, thus increasing the therapeutic window and addressing indications not accessible by current therapies.