On December 9, 2019 Biocept, Inc. (NASDAQ: BIOC) ("Biocept" or the "Company"), a leading commercial provider of liquid biopsy solutions, reported the pricing of an underwritten public offering of 24,600,000 shares of its common stock (or pre-funded warrants to purchase common stock in lieu thereof) and warrants to purchase up to 24,600,000 shares of the Company’s common stock (Press release, Biocept, DEC 9, 2019, View Source [SID1234552163]). Each share of common stock or pre-funded warrant is being sold together with one warrant to purchase one share of common stock at a combined price to the public of $0.405 per share and warrant. Gross proceeds, before underwriting discounts and commissions and estimated offering expenses, are expected to be approximately $10.0 million.

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The warrants will be immediately exercisable at a price of $0.405 per share of common stock and will expire five years from the date of issuance. Additionally, if the volume-weighted average price of our common stock is below the exercise price per share of the warrants on any trading day beginning the earlier of (i) 30 days from today, and (ii) the trading day on which the aggregate trading volume of our common stock is equal to more than three times the number of shares of common stock sold in the offering, then the warrantholders may elect to cashless exercise their warrants for a number of shares equal to 50% of the shares issuable upon cash exercise. Each pre-funded warrant has an exercise price of $0.01 per share, is exercisable immediately and will expire when exercised in full. The shares of common stock or the pre-funded warrants and the accompanying warrants, can only be purchased together in the offering, but will be issued separately and will be immediately separable upon issuance. The offering is expected to close on or about December 11, 2019, subject to customary closing conditions.

Maxim Group LLC is acting as the book-running manager and Dawson James Securities, Inc. is acting as a co-manager in connection with the offering.

Biocept also has granted to Maxim Group LLC a 45-day option to purchase up to an additional 3,690,000 shares of common stock and/or warrants to purchase up to 3,690,000 shares of common stock, at the public offering price less discounts and commissions.

The offering is being conducted pursuant to the Company’s registration statement on Form S-1 (File No. 333-234459), as amended, previously filed with and subsequently declared effective by the Securities and Exchange Commission ("SEC"). A final prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at View Source Electronic copies of the final prospectus relating to this offering, when available, may be obtained from Maxim Group LLC, 405 Lexington Avenue, 2nd Floor, New York, NY 10174, at (212) 895-3745.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall 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 the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 9, 2019 BJ Bioscience Inc. (the ‘company’) reported that the first patient was successfully dosed on December 4, 2019 in the first-in-human (FIH) trial of the company’s BJ-001 program at NEXT ONCOLOGY in San Antonio, Texas (Press release, BJ Bioscience, DEC 9, 2019, View Source [SID1234552188]).

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"We were so excited to learn the successful dosing of the first patient for our BJ-001 program. It marked a significant milestone for BJ Bioscience and for the BJ-001 program. With its tumor targeting property, BJ -001 is expected to benefit many cancer patients with integrin overexpression. The successful dosing of the first patient is a small but key step of testing this promising investigational drug," said Joe Zhang, MD. Ph.D., DABT, the co-founder and CEO of BJ Bioscience. "With strong support from our investor, we will soon initiate trials in China to speed up the development of this drug candidate globally."

The ongoing first-in-human study is an open-label, Phase 1a trial in locally advanced/metastatic or relapsed/refractory solid tumors utilizes an accelerated dose escalation design followed by a traditional 3+3 dose escalation algorithm to assess the safety and tolerability of BJ-001, to identify the MTD, and/or and RP2D of BJ-001 as a single agent and in combination with an anti-PD-1 antibody.

"We achieved this milestone with approximately 3 months after we received the ‘green light’ from the FDA. More proudly, we achieved FPI milestone with 3 days after the site was activated. It is exceptional based on my past experience in multinational pharmaceutical companies," commented Grace Yu, MD., VP of Clinical Development at BJ Bioscience. "It is a great example of successful team work. The team had been working diligently for this milestone. Thanks go to our colleagues at Next Oncology as well as the patient. We cannot achieve this milestone without the hard work and collaboration of each of the members."

"As of 08 Dec 2019, the patient has been completed C1D5. No CRS and no other adverse events have been observed." said Dr. Raghad Abdul Karim, Medical Oncologist, Hematologist, Principle Investigator of BJ-001-01-001US study, NEXT Oncology.

About BJ-001

BJ-001 is the first tumor targeting IL-15 fusion protein in the world. It is designed to target cancer cells that overexpress integrins such as αvβ3, αvβ5, and αvβ6 by its tumor targeting motif and to stimulate anti-cancer immunity by its IL-15 motif. Such design has a potent to increase anti-cancer effects and reduce systemic toxicity by localizing IL-15’s effects in tumor microenvironment. Many cancer types such as NSCLC, stomach cancer, and pancreatic cancer have been shown to overexpress integrin.

On December 8, 2019 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported new in vivo preclinical data for FT596, its off-the-shelf, multi-antigen targeting natural killer (NK) cell product candidate derived from a clonal master engineered induced pluripotent stem cell (iPSC) line (Press release, Fate Therapeutics, DEC 8, 2019, View Source [SID1234552041]). The data were featured during the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition as part of the organization’s CAR-T and Beyond press program, which spotlighted promising next-generation cancer immunotherapies having the potential to overcome the key limitations of patient-specific chimeric antigen receptor (CAR) T-cell therapy.

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"Current patient- and donor-specific CAR T-cell immunotherapies recognize only one antigen and fail to address the significant risk of relapse due to antigen escape. FT596 is ground-breaking in that it is designed to be available off-the-shelf for timely patient access and to promote deeper and more durable responses by targeting multiple tumor-associated antigens," said Bob Valamehr, Ph.D., Chief Development Officer of Fate Therapeutics. "Additionally, since FT596 is manufactured from a renewable master engineered iPSC line, the complexities of patient-by-patient genetic engineering and production are greatly reduced and, for the first time, we are able to mass produce multi-functional cellular immunotherapies in a uniform and cost-effective manner."

FT596 is the first cellular immunotherapy engineered with three active anti-tumor components to be cleared for clinical investigation by the FDA. In addition to a proprietary CAR targeting CD19, FT596 expresses a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity, enabling coincident targeting of CD19 and additional tumor-associated antigens such as CD20. FT596 also expresses an interleukin-15 receptor fusion (IL-15RF), a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support. Together, these features of FT596 are intended to maximize potency and minimize toxicity in treated patients. The Company plans to initiate enrollment of a first-in-human clinical trial of FT596 in early 2020.

New preclinical data presented at ASH (Free ASH Whitepaper) showed that FT596 administered as a monotherapy exhibited durable tumor clearance and extended survival in vivo similar to primary CAR T cells in a humanized mouse model of CD19+ lymphoma. Additionally, when combined with the anti-CD20 monoclonal antibody rituximab, FT596 showed enhanced killing of CD20+ lymphoma cells in vivo as compared to rituximab alone. These data confirm previously presented in vitro findings that demonstrate the unique multi-antigen targeting functionality of FT596, and the product candidate’s potential to effectively overcome CD19 antigen escape.

The Company also announced that, in preparation for Phase 1 initiation, it had recently completed GMP production of FT596. In a single small-scale manufacturing campaign, the Company produced over 300 cryopreserved, infusion-ready doses of FT596 at a cost of approximately $2,500 per dose. The Company’s iPSC product platform unites stem cell biology and precision genetic engineering to create renewable master engineered iPSC lines that can be repeatedly used to mass produce cancer-fighting immune cells, replacing the high production costs, weeks of manufacturing time, and complex manufacturing processes required for current-generation CAR T-cell immunotherapies with a lower-cost, easier-to-manufacture, well-characterized, off-the-shelf product that has the potential to reach many more patients.

FT596 is the third off-the-shelf, iPSC-derived NK cell product candidate from the Company’s proprietary iPSC product platform cleared for clinical investigation by the FDA in the past twelve months. On Saturday, the Company announced that the first patient treated for acute myeloid leukemia in its Phase 1 clinical trial of FT516, an off-the-shelf, iPSC-derived NK cell cancer immunotherapy engineered to express hnCD16, showed no morphologic evidence of leukemia, chimerism of FT516 in the bone marrow, and hematopoietic recovery, including complete neutrophil recovery without growth factor support (>1,000 per µL), after receiving three once-weekly doses of FT516 and IL-2 cytokine support.

On December 8, 2019 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company") shared new, reported that long-term data from the pivotal Phase III trial of Lumoxiti (moxetumomab pasudotox-tdfk) at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, USA, which expands on the efficacy results and affirms the manageable safety profile of the medicine (Press release, Innate Pharma, DEC 8, 2019, View Source [SID1234552026]).

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The final analysis showed that 36 percent (29/80) of the relapsed or refractory hairy cell leukemia patients achieved durable complete response (CR) with Lumoxiti at Day 181 of patients’ respective evaluation, compared to the primary analysis in which 30 percent durable CR rate was reported. In addition, there was a 61 percent probability that patients who achieved a CR would maintain it after five years.

"Lumoxiti is a first-in-class medicine and the only treatment approved in the US for relapsed or refractory hairy cell leukemia in more than twenty years; therefore, it is important for the hematology-oncology community to receive additional analysis of its long-term efficacy," commented Pierre Dodion, MD, Executive Vice President and Chief Medical Officer of Innate Pharma. "We are grateful to the patients and health care professionals who participated in the clinical development of Lumoxiti and we are passionate about continuing to address the unmet need in this rare form of cancer."

The single-arm, multi-center, open-label Phase III ‘1053’ clinical trial assessed the efficacy, safety, immunogenicity and pharmacokinetics of Lumoxiti monotherapy in 80 patients with relapsed or refractory hairy cell leukemia who had received at least two prior therapies, including one purine nucleoside analog. The primary endpoint of durable CR was defined as CR with hematologic remission (HR) for >180 days.

Findings from the final analysis of the Lumoxiti Phase III trial include:

Efficacy measure

Result* (n=80, 95% Confidence Interval)

Durable CR (CR with HR > 180 days)

36.3% (25.8 to 47.8)

CR with HR ≥ 360 days

32.5% (22.4 to 43.9)

CR rate

41.3% (30.4 to 52.8)

CR with MRD-negative status

33.8% (23.6 to 45.2)

Partial Response Rate

33.8%

Hematologic Remission Rate

80.0%

Median duration of CR

62.8 months (0.0+ to 62.8)

Median Progression-Free Survival

41.5 months (range 0.0+ to 71.7)

* BICR = blinded independent central review

"A key treatment goal for patients with relapsed or refractory hairy cell leukemia is to achieve sustained remission, which can be particularly challenging in patients in whom prior therapies have failed. This long-term analysis demonstrates that Lumoxiti achieved a high rate of durable efficacy, while maintaining the benefit risk profile we saw in the primary analysis," said Robert J. Kreitman, MD, Senior Investigator, Head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, and Principal Investigator of the Phase III clinical trial.

The final analysis shows that the risk-benefit profile of Lumoxiti is maintained. There were no new serious adverse events and no change in hemolytic uremic syndrome or capillary leak syndrome. Per the primary analysis on the 1053 study, the most frequent treatment-related adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), headache (33%), and pyrexia (31%). Treatment-related grade 3/4 AEs were reported in 24 patients (30%) and treatment-related serious AEs in 14 patients (18%). Grade 3/4 CLS events occurred in two patients (2.5%) and any grade of HUS occurred in six patients (7.5%). CLS and HUS events were manageable and reversible with appropriate supportive care and monitoring.

Treatment-emergent AEs led to study drug discontinuation in eight patients (10.0%): hemolytic uremic syndrome (HUS), n = 4 (5.0%); capillary leak syndrome (CLS), n = 2 (2.5%); increased blood creatinine, n = 2 (2.5%); renal failure, n =1 (1.3%); vomiting, n =1 (1.3%); and chills, n =1 (1.3%). There were four deaths reported (including the three reported during the primary analysis): two due to disease progression and two due to an AE (1 each of pneumonia and septic shock). No death was considered treatment related.

On December 8, 2019 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for the treatment of cancer, reported clinical and regulatory updates for its lead drug candidate, tipifarnib, in angioimmunoblastic T-cell lymphoma (AITL), including data from the Company’s ongoing Phase 2 clinical trial of tipifarnib in relapsed or refractory peripheral T-cell lymphoma (PTCL) (Press release, Kura Oncology, DEC 8, 2019, View Source [SID1234552042]). The updated interim data are being presented during an oral session today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting in Orlando. A copy of the presentation is available on the Company’s website at www.kuraoncology.com.

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"Tipifarnib continues to demonstrate clinically meaningful activity in advanced PTCL, including patients with AITL for whom there are few treatment options," said Thomas Witzig, M.D., a Hematologist at Mayo Clinic and a principal investigator in the trial. "The high level of clinical activity of tipifarnib, including complete responses, in third- and fourth-line patients, coupled with the fact that tipifarnib is an oral medication means it could be another treatment option for a patient population with high unmet need."

In June 2019, Kura reported that the primary efficacy endpoint was achieved in each of the expansion cohorts in its Phase 2 trial of tipifarnib in relapsed or refractory PTCL: 1) patients with AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression, and 2) patients with PTCL who lack a single nucleotide variation in the 3’-untranslated region of the CXCL12 gene. Given the high level of activity observed among AITL patients, Kura continued to enroll patients to acquire more experience regarding safety and tolerability in this population. Based upon the 2016 revision of the World Health Organization classification of lymphoid neoplasms1, AITL and AITL-like histologies represent approximately one-third of all PTCL cases.

As of the November 11, 2019 data cutoff date, a total of 26 patients with relapsed or refractory AITL were enrolled in all stages of the trial. Among the 20 patients evaluable for efficacy, five achieved a complete response (CR) and five achieved a partial response (PR), for an objective response rate (ORR) of 50% on an evaluable basis and 38% on an intent-to-treat basis. In addition, three patients experienced disease stabilization. Patients had a median of three prior regimens (range 1-7).

Next-generation sequencing of 19 available patient biopsies showed that 10 (53%) carried C336R/Q386E variants in the killer-cell immunoglobulin-like receptor (KIR) 3DL2, an immune checkpoint receptor. Four of the 10 patients with KIR3DL2 variants achieved a CR and three achieved a PR, for a CR rate of 40% and an ORR of 70%. This compares to a CR rate of 11% and an ORR of 22% among the nine AITL patients with KIR3DL2 wild type.

Tipifarnib was generally well-tolerated in this Phase 2 trial, with adverse events consistent with its known safety profile. The most frequently observed treatment-related adverse events (grade ≥ 3) were hematology-related, including thrombocytopenia, neutropenia, leukopenia, anemia, febrile neutropenia and lymphopenia.

"We are encouraged by our growing body of data for tipifarnib in AITL," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "We believe these data support our efforts to expand the development of tipifarnib beyond our initial focus in HRAS mutant solid tumors and could enable registrational strategies in multiple CXCL12-dependent hematologic and solid tumor indications."

Regulatory Update

Following FDA feedback from an end-of-Phase 2 (EOP2) meeting, Kura plans to initiate a Phase 2 registration-directed trial of tipifarnib in patients with relapsed or refractory AITL and related lymphomas in 2020. The multi-center, single-arm trial will target enrollment of 128 patients with AITL and AITL-like histologies who are relapsed or refractory to at least one prior systemic cytotoxic therapy.

The trial has two independent primary objectives: 1) Efficacy in terms of ORR in all patients enrolled and 2) Efficacy in terms of ORR in patients who carry KIR3DL2 variants. Patients will be enrolled on the basis of a pathological diagnosis of AITL and AITL-like histologies, and KIR3DL2 mutational status will be determined retrospectively. Each of the two primary objectives has a null hypothesis of 9%, and each one can be met independently. FDA EOP2 meeting minutes indicate that the trial, as designed, may be adequate to support an NDA seeking accelerated approval of tipifarnib in AITL and AITL-like histologies, and/or AITL and AITL-like histologies with KIR3DL2 mutations.

"We are grateful for the regulatory feedback from the FDA on our single-arm trial design, providing an opportunity for a potential path for accelerated approval for tipifarnib in AITL and AITL-like histologies, an indication of significant unmet need and one for which they are no FDA approved therapies," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Consistent with our development strategy in HRAS mutant solid tumors, we have chosen to focus initially on AITL and AITL-like histologies, an indication that can be pursued with small, single-arm, registration-directed study. Once we establish a foothold there, we expect to see a clear path to expand the potential commercial opportunity by moving both to earlier lines of therapy and expanding to additional CXCL12-driven hematologic malignancies and solid tumor indications."

About Angioimmunoblastic T-Cell Lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of T-cell lymphoma frequently characterized by high levels of CXCL12 expression. Significant advances in the genetic landscape of T-cell and NK-cell neoplasms as the result of genomic studies, as well as the introduction of more powerful diagnostic technologies have led to revisions in the classification and introduction of new entities. Many of the same genetic changes observed in AITL are also observed in cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) that manifest a T follicular helper (TFH) phenotype. This common genotype/phenotype has led to follicular T-cell lymphoma (FTCL) and AITL being unified under a common heading. Cases of nodal PTCL with TFH phenotype are now included in the same grouping as well. As a result, patients with the PTCL-NOS phenotype are increasingly being characterized as having AITL and/or AITL-like histologies.

About Tipifarnib

Kura Oncology’s lead drug candidate, tipifarnib, is a potent, selective and orally bioavailable inhibitor of farnesyl transferase in-licensed from Janssen in December 2014. Previously, tipifarnib was studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets; however, no molecular mechanism of action had been determined that could explain its clinical activity across a range of solid tumor and hematologic indications. Leveraging advances in next generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura is seeking to identify those patients most likely to benefit from tipifarnib. Kura initiated its first Phase 2 registration-directed trial of tipifarnib in patients with recurrent or metastatic HRAS mutant head and neck squamous cell carcinoma (HNSCC) in November 2018. Later that month, the U.S. Patent and Trademark Office issued a new patent for tipifarnib as a method of treating patients with AITL, providing exclusivity in the United States to 2037.