On February 27, 2020 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2019 (Press release, Intellia Therapeutics, FEB 27, 2020, View Source [SID1234554863]).

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"In 2019, we advanced our full-spectrum strategy, guiding both our in vivo and ex vivo lead programs toward the clinic. We also continued to build on our genome editing and delivery capabilities to enable a rapid succession of candidates," said Intellia President and Chief Executive Officer, John Leonard, M.D. "We are off to a productive start in 2020. We announced the nomination of NTLA-5001, a WT1-directed TCR-T cell therapy for the treatment of AML, and plan to select our third development candidate in the first half of this year, which will be for the treatment of HAE. In addition, in the second half of the year, we expect to begin dosing ATTR patients with NTLA-2001, a potential single-course treatment for ATTR patients. This is anticipated to be the first-ever systemically delivered CRISPR/Cas9-based therapy to enter the clinic, representing an important milestone in our mission to deliver potentially curative therapies from our proprietary modular platform."

2019 and Recent Operational Highlights

ATTR Program: Intellia remains on track to submit an investigational new drug (IND) application in mid-2020 for its lead in vivo candidate, NTLA-2001, for the treatment of transthyretin amyloidosis (ATTR). In December 2019, Intellia completed a 12-month durability study of its lead lipid nanoparticle (LNP) formulation in support of NTLA-2001, maintaining an average reduction of >95% of serum transthyretin (TTR) protein and sustained liver genome editing after a single dose in non-human primates (NHPs). NTLA-2001 is anticipated to be the first systemically delivered CRISPR/Cas9 therapy to enter the clinic, and Intellia expects to dose the first patients in the second half of 2020. NTLA-2001 is part of a co-development/co-promotion (Co/Co) agreement between Intellia, which is the lead development and commercialization party, and Regeneron Pharmaceuticals, Inc. (Regeneron).
AML Program: In January 2020, Intellia announced NTLA-5001 as its first engineered T cell therapy development candidate for the treatment of acute myeloid leukemia (AML). NTLA-5001 utilizes a T cell receptor (TCR)-directed approach to target the Wilms’ Tumor 1 (WT1) intracellular antigen to develop a broadly applicable treatment for AML patients, regardless of mutational background of a patient’s leukemia. At the recent Keystone Symposia’s Engineering the Genome Conference, the Company presented data in support of NTLA-5001, demonstrating that the selection of a naturally-occurring, high-affinity TCR, in combination with Intellia’s CRISPR-enabled engineering and targeted insertion, results in an engineered T cell capable of specific and potent killing of primary AML blasts. Importantly, data presented showed that CRISPR-enabled engineering overcomes certain key challenges of traditional TCR approaches, such as mispairing between therapeutic and endogenous TCR, therefore creating a more homogenous T cell product. The engineered T cell carrying the therapeutic TCR also exhibited no detectable off-target reactivity to bone marrow cells. The Company plans to submit an IND application for NTLA-5001 in the first half of 2021. Additional efforts are underway to evaluate the potential use of the WT1-directed TCR construct to treat other tumor types, including solid tumors.
HAE Program: In January 2020, Intellia announced hereditary angioedema (HAE) as its third development program. Building on the modular LNP delivery platform developed in the ATTR program, the Company aims to knock out the kallikrein B1 (KLKB1) gene with a single course of treatment to reduce the spontaneous activation of biological pathways responsible for generating bradykinin and thereby ameliorate the frequency and intensity of HAE attacks. At the recent Keystone Conference, the Company reported results from an ongoing NHP study, which demonstrated a 90% reduction in kallikrein activity sustained for at least five months following a single dose. The reduction of kallikrein activity observed in this study corresponds to the reduced enzymatic levels in patients that meaningfully impact HAE attack rates (Source: Banerji et al., NEJM, 2017). Intellia expects to select its development candidate in the first half of 2020. Intellia’s KLKB1 HAE program is subject to an option by Regeneron to enter into a Co/Co agreement prior to the initiation of IND-enabling studies, with Intellia as the lead party.
Modular Platform: Intellia continued to progress differentiated genome editing and delivery strategies, including targeted insertion and consecutive editing, across its in vivo and ex vivo efforts. These platform capabilities enable the removal and/or restoration of a gene’s function in developing treatments for life-threatening diseases. In 2019, the Company demonstrated the first CRISPR-mediated, targeted transgene insertion in the liver of NHPs. The targeted insertion of the Factor 9 gene generated circulating human Factor IX protein at or above normal levels. Additionally, Intellia presented the first demonstration of a consecutive in vivo gene knockout followed by a targeted insertion in an alpha-1 antitrypsin deficiency (AATD) mouse model. The consecutive edits led to >98% reduction of the disease-causing protein and sustained restoration of the normal protein to therapeutically relevant circulating levels throughout the study. The Company continues to advance these platform capabilities and leverage them to develop the next wave of in vivo and ex vivo clinical candidates.
Board of Directors Update: Dr. Frank Verwiel was elected Chairman of the Board of Directors in February 2020, succeeding Perry Karsen, who will remain a member of the Board.
Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR:
Submit IND application for NTLA-2001 in mid-2020
Dose first patients in 2H 2020
AML:
Submit IND application for NTLA-5001 in 1H 2021
HAE:
Nominate a development candidate in 1H 2020
R&D Advancements:
Present preclinical data at upcoming scientific conferences in 2020
Upcoming Event

The Company will participate in the following investor event during the first quarter of 2020:

Barclays Capital Global Healthcare Conference, March 10, Miami
Fourth Quarter and Full Year 2019 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $284.5 million as of December 31, 2019, compared to $314.1 million as of December 31, 2018. The decrease was driven by cash used to fund operations of approximately $124.9 million, which was offset in part by $72.3 million of net equity proceeds raised from the Company’s "At the Market" (ATM) offerings, $9.0 million of funding received under the Novartis collaboration, $9.9 million of ATTR cost reimbursements made by Regeneron, and $4.2 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue increased by approximately $3.1 million to $10.9 million during the fourth quarter of 2019, compared to $7.9 million during the fourth quarter of 2018. The increase in collaboration revenue in 2019 was primarily driven by amounts recognized under the Company’s ATTR Co/Co agreement with Regeneron. As previously disclosed, Regeneron funded approximately 50% of the development costs for the ATTR program throughout 2019. Starting in June 2020, Regeneron will share approximately 25% of worldwide development costs and commercial profits for the ATTR program.
R&D Expenses: Research and development expenses increased by $11.8 million to $31.7 million during the fourth quarter of 2019, compared to $19.9 million during the fourth quarter of 2018. This increase was mainly due to IND-enabling activities for NTLA-2001, research efforts supporting the selection of NTLA-5001 and the expansion of the Company’s research and development team.
G&A Expenses: General and administrative expenses increased by $0.3 million to $9.0 million during the fourth quarter of 2019, compared to $8.7 million during the fourth quarter of 2018. This increase was driven primarily by employee-related expenses.
Net Loss: The Company’s net loss was $28.3 million for the fourth quarter of 2019, compared to $19.1 million during the fourth quarter of 2018.
Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of December 31, 2019 will enable the Company to fund its anticipated operating expenses and capital expenditure requirements at least through the end of 2021. This expectation excludes any strategic use of capital not currently in the Company’s base-case planning assumptions.

Conference Call to Discuss Fourth Quarter and Full Year 2019 Earnings

The Company will discuss these results on a conference call today, February 27, 2020, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-877-317-6789 and use conference ID# 10138773, approximately five minutes before the call.
International callers should dial 1-412-317-6789 and use conference ID# 10138773, approximately five minutes before the call.
A replay of the call will be available through the Events and Presentations page of the Investor Relations section on Intellia’s website, beginning on February 27, 2020 at 12 p.m. ET.

On February 27, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that it has entered into a common stock purchase agreement (the "Agreement") of up to $30 million with Aspire Capital Fund, LLC ("Aspire Capital") (Press release, Curis, FEB 27, 2020, View Source [SID1234554861]).

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Under the terms of the Agreement, Aspire Capital has made an initial investment of $3 million via purchase of 2,693,965 common shares of Curis. In addition, Aspire Capital has committed to purchasing up to $27 million of common shares of Curis, at Curis’ request from time to time during a 30-month period at prices based on the market price at the time of each sale, subject to certain limits. There are no warrants, derivatives, or other share classes associated with this Agreement. Curis will control the timing and amount of the further sale of its common shares to Aspire Capital.

"We are excited to enter into this transaction with Aspire Capital, a long-term, healthcare-focused institutional investor," said James Dentzer, President and Chief Executive Officer of Curis. "This facility is expected to provide us with a flexible, efficient capital source to advance the clinical development of our novel, targeted cancer therapeutics, including fimepinostat, a small molecule dual inhibitor of PI3K/HDAC and suppressor of MYC; CA-4948, an IRAK4 kinase inhibitor and first in class suppressor of the TLR pathway and CI-8993, a first in class VISTA antagonist."

"Curis’ pipeline of novel, targeted cancer therapies and immunotherapies, bolstered by the recent addition of CI-8993, addresses therapeutics areas with significant unmet medical need and patient burden," stated Steven G. Martin, Managing Member of Aspire Capital Partners, LLC. "Aspire is pleased to support Curis at this transformational time and looks forward to this long-term partnership with the Curis team."

Proceeds will be used by Curis for general corporate purposes, including research and development, clinical trial activity and working capital. There are no restrictions on future financings and there are no financial covenants, participation rights, rights of first refusal, or penalties in the Agreement. Curis has the right to terminate the Agreement at any time without any additional cost or penalty.

As consideration for Aspire Capital’s obligation under the Agreement, Curis issued 646,551 common shares to Aspire Capital as a commitment fee. Curis also entered into a Registration Rights Agreement with Aspire Capital in connection with its entry into the Agreement. A complete and detailed description of the Agreement and the related Registration Rights Agreement is set forth in Curis’ Current Report on the Form 8-K filed today with the U.S. Securities and Exchange Commission (SEC).

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities nor will there be any sale of these securities in any state or other 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 other jurisdiction.

On February 27, 2020 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biopharmaceutical company with a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported new pre-clinical findings in connection with its on-going collaboration with Univo Pharmaceuticals (TASE:UNVO), demonstrating CBD’s robust anti-neoplastic effect in pre-clinical studies against liver cancer (Press release, Can-Fite BioPharma, FEB 27, 2020, View Source [SID1234554860]). The studies were carried out on human liver cancer cells and utilized cannabinoid fractions enriched for CBD, in nano and pico molar concentrations. Marked inhibition of Hep-3b, liver cancer cell proliferation was noted and was mediated via the A3 adenosine receptor, the target of Can-Fite’s drug platform.

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Can-Fite is greatly encouraged and sees clinical potential in treating patients with minute CBD dosages which are effective and at the same time may minimize potential adverse effects. Based on this approach, an expansion of the agreement with Univo Pharmaceuticals has been entered into to allow the testing of minute CBD concentrations/dosages in combination with Namodenoson on liver cancer and additional oncological indications. As part of the expansion, Can-Fite will fund the research and development activities for the two new indications, to be jointly performed, for an amount of US$200,000 per indication.

Dr. Michael Silverman, M.D., Can Fite Medical Director, commented on the new findings, "Many of the liver cancer patients are already treated with cannabinoids for management of constitutional symptoms such as anorexia, nausea, and fatigue. These novel findings of anti-cancer cell effects found with minute dosages of CBD may open up new avenues of utilizing cannabinoids to treat cancer patients while minimizing adverse effects."

According to Adroit Market Research, the medical cannabis market is projected to grow at a CAGR of 29% to $56.7 billion by 2026.

On February 27, 2020 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a late clinical-stage biopharmaceutical company focused on oncology, reported that a Notice of Allowance has been issued by the United States Patent and Trademark Office (USPTO) for a patent application claiming the use of motixafortide (BL-8040), a novel immunotherapy compound, combined with any PD-1 inhibitor, for the treatment of any type of cancer (Press release, BioLineRx, FEB 27, 2020, View Source [SID1234554859]).

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The PD-1 antagonist can be any agent that prevents and/or inhibits the biological function and/or expression of PD-1, such as pembrolizumab (KEYTRUDA). The targeted cancer can be solid, non-solid, and/or a cancer metastasis.

This patent, when issued, will be valid until July 2036 with a possibility of up to five years patent term extension. Additional corresponding patent applications are pending in Europe, Japan, China, Canada, Australia, India, Korea, Mexico, Brazil and Israel.

"We are extremely pleased to receive this valuable notice of allowance from the USPTO, which entitles us to long-term, highly enforceable and broad patent protection for our lead product, motixafortide, in combination with any PD-1 inhibitor, and more importantly, for all cancer indications, including, of course, any solid tumor," stated Philip Serlin, Chief Executive Officer of BioLineRx. "This important patent allowance also supports our ongoing Phase 2a COMBAT/KEYNOTE-202 trial in stage IV metastatic pancreatic cancer patients, for which we have recently completed patient recruitment in the triple combination arm investigating the safety, tolerability and efficacy of motixafortide, KEYTRUDA and chemotherapy. Following promising initial results demonstrating robust and durable responses to the triple combination treatment, we look forward to the progression-free and overall survival data from the triple combination arm expected in mid-2020."

The COMBAT/KEYNOTE-202 Study
The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multicenter, single-arm trial to evaluate the safety and efficacy of the dual combination of motixafortide and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 30 subjects with metastatic pancreatic adenocarcinoma. The study was primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and was carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include the triple combination arm investigating the safety, tolerability and efficacy of motixafortide, KEYTRUDA and chemotherapy as part of the Phase 2a COMBAT/KEYNOTE-202 study. In January 2020, the Company announced completion of recruitment of the 40 patients planned for the triple combination arm of the study.

About Motixafortide in Cancer Immunotherapy
Motixafortide is targeting CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

Motixafortide is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

In a number of clinical and preclinical studies, motixafortide has been shown to affect multiple modes of action in "cold" tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor niche, turning "cold" tumors, such as pancreatic cancer, "hot" (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

On February 27, 2020 GlaxoSmithKline plc reported that the European Medicines Agency (EMA) has validated the company’s Type II Variation (T2V) for Zejula (niraparib) as a maintenance treatment in the first-line setting for women with advanced ovarian cancer who responded to platinum-based chemotherapy regardless of biomarker status (Press release, GlaxoSmithKline, FEB 27, 2020, View Source [SID1234554851]). Validation of the T2V confirms that the submission is accepted and begins the formal review process by the EMA’s Committee for Human Medicinal Products (CHMP).

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The submission is based on data from the PRIMA study (ENGOT-OV26/GOG-3012), which demonstrated clinically meaningful outcomes of niraparib treatment in the first-line maintenance setting.[1] Results from the PRIMA study were presented at the 2019 European Society for Medical Oncology Congress and simultaneously published in the New England Journal of Medicine. The PRIMA study enrolled women who responded to first-line treatment with platinum-based chemotherapy, including those with high risk of disease progression, a population with high unmet need and previously under-represented in first-line ovarian cancer studies.

In Europe, ovarian cancer is the sixth deadliest cancer among women and more than 65,000 women are diagnosed each year.[2] Most women are diagnosed with advanced (stage III or IV) ovarian cancer and have a five-year survival rate of ~30%.[3] Despite high response rates to platinum-based chemotherapy in the first-line, approximately 85% of women with advanced ovarian cancer will see their disease return.[4] With each recurrence, the time a woman may spend without her cancer progressing until the next recurrence gets shorter.

About PRIMA

PRIMA is a double-blind, randomised Phase III study designed to evaluate niraparib versus placebo in women being treated first-line for stage III or IV ovarian cancer. The study assessed the efficacy of niraparib as maintenance therapy, as measured by progression free survival. Patients in complete or partial response to first-line platinum-based chemotherapy were randomised 2:1 to niraparib or placebo.

About Zejula (niraparib)

Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies, including a Phase III study as a first-line triplet maintenance treatment in ovarian cancer (FIRST).

Important Information for ZEJULA
Zejula approved indication:

Zejula is indicated as monotherapy for the maintenance treatment of adult patients with platinum‑sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum‑based chemotherapy.

Important Safety Information
Contraindications: Hypersensitivity to niraparib or to any of the excipients and breast-feeding.

Warnings and precautions: Test complete blood counts weekly for the first month of treatment, then monthly thereafter. If a patient develops severe persistent haematologic toxicity including pancytopenia that does not resolve within 28 days following interruption, Zejula should be discontinued. Due to the risk of thrombocytopenia, anticoagulants and medicinal products known to reduce the thrombocyte count should be used with caution. If MDS and/or AML are confirmed while being prescribed Zejula , treatment should be discontinued, and the patient treated appropriately. Hypertension, including hypertensive crisis, has been reported with the use of Zejula. Pre‑existing hypertension should be adequately controlled before starting Zejula treatment. Zejula should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy. Patients with galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine. Tartrazine may cause allergic reactions. Paediatric safety and efficacy has not yet been established.

Undesirable effects: The most common serious adverse reactions were thrombocytopenia and anaemia.

Very common (≥1/10): urinary tract infection, thrombocytopenia, anaemia, neutropenia, decreased appetite, insomnia, headache, dizziness, dysgeusia, palpitations, hypertension, dyspnea, cough, nasopharyngitis, nausea, constipation, vomiting, abdominal pain, diarrhoea, dyspepsia, back pain, arthralgia, fatigue, asthenia.

Common (≥1/1000 to <1/10): bronchitis, conjunctivitis, leukopenia, hypokalemia, anxiety, depression, tachycardia, epistaxis, dry mouth, abdominal distension, mucosal inflammation (including mucositis), stomatitis, photosensitivity, rash, myalgia, oedema peripheral, Gamma-glutamyl transferase increased, AST increased, blood creatinine increased, ALT increased, blood alkaline phosphatase increased, weight decreased.

Refer to the Zejula Prescribing Information for a full list of adverse events and the complete important safety information.

GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.