On November 14, 2019 Replimune Group, Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported the pricing of its public offering of 3,678,031 shares of its common stock at a public offering price of $13.61 per share (Press release, Replimune, NOV 14, 2019, View Source [SID1234551296]). In addition, and in lieu of common stock, Replimune reported the pricing of its public offering of pre-funded warrants to purchase 2,200,000 shares of its common stock at a purchase price of $13.6099 per pre-funded warrant, which equals the public offering price per share of the common stock less the $0.0001 per share exercise price of each pre-funded warrant. The aggregate gross proceeds from the offering are expected to be approximately $80 million, before deducting the underwriting discounts and commissions and estimated offering expenses payable by Replimune. All of the shares of common stock and pre-funded warrants are being offered by Replimune. In addition, Replimune has granted the underwriters a 30-day option to purchase up to an additional 881,704 shares of its common stock from Replimune at the public offering price, less the underwriting discounts. The offering is expected to close on November 18, 2019, subject to the satisfaction of customary closing conditions.

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J.P. Morgan Securities LLC, SVB Leerink LLC, and BMO Capital Markets Corp. are acting as book-running managers for the offering. Wedbush Securities Inc. is acting as co-lead manager and Roth Capital Partners, LLC is acting as co-manager for the offering.

A preliminary prospectus supplement and a free writing prospectus relating to and describing the terms of the offering were filed with the Securities and Exchange Commission (the "SEC") on November 12, 2019 and November 13, 2019, respectively. The final prospectus supplement relating to the offering will be filed with the SEC. Copies of the final prospectus supplement relating to the offering may be obtained, when available, by visiting EDGAR on the SEC website at www.sec.gov or from: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204, or by e-mail at [email protected]; SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132, or by e-mail at [email protected]; or BMO Capital Markets Corp., Attention: Equity Syndicate Department, 3 Times Square, 25th Floor, New York, NY 10036, by telephone at (800) 414-3627 or by e-mail at [email protected].

The shares of common stock and the pre-funded warrants described above are being offered by Replimune pursuant to its shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Replimune with the SEC on August 8, 2019 and declared effective by the SEC on August 15, 2019. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 14, 2019 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported its business update for the quarter ending September 30, 2019 (Press release, Transgene, NOV 14, 2019, View Source [SID1234551312]).

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Key events of the third quarter 2019

TG4001: Promising Phase 1b data in patients with HPV-positive cancers presented at ESMO (Free ESMO Whitepaper) at the end of September. Combination regimen of Transgene’s therapeutic vaccine TG4001 and avelumab showed durable partial responses in 3 of the 6 difficult-to-treat patients treated with the higher dose of TG4001 (more than 30% reduction in tumor size). These data suggest that this TG4001 based combination could provide a much-improved treatment option for patients who receive second-line treatment for HPV-positive cancers. The median overall survival with currently available treatments remains below 11 months and median progression-free survival is between 2 and 4 months; overall response rates are around 10-15%.
The data presented at ESMO (Free ESMO Whitepaper) also confirmed that TG4001 stimulated the immune system and favorably modified the tumor micro-environment, an element that is key in the success of immunotherapies. The Phase 2 part of the trial is ongoing; interim Phase-2 data are expected during the first half of 2020.
TG4050: Transgene received approvals to start the first clinical trials with myvac from the UK and French health authorities (MHRA and ANSM). The FDA clearance to proceed with a trial of TG4050 was obtained in May 2019. Both Phase 1 clinical trials of TG4050, in the US and Europe, are expected to start before the end of the year.
TG6002: Transgene received approval from the MHRA (UK) to start a Phase 1/2 clinical trial with TG6002 administered via an intrahepatic artery (IHA) infusion in colorectal cancer patients with unresectable liver metastases. The IHA route of administration is expected to deliver TG6002 to the tumor at a higher hepatic concentration to increase efficiency while limiting systemic exposure to patients. This is in addition to the ongoing Phase 1/2 study that is evaluating TG6002 when given via the intravenous (IV) route in patients with CRC. The trial is expected to begin before the end of 2019.
Pexa-Vec: On August 2, 2019, Transgene announced that the Independent Data Monitoring Committee (IDMC) of the PHOCUS Phase 3 trial in HCC recommended that SillaJen stop the study based on the IDMC’s assessment that the trial was unlikely to meet its primary objective at the time of the final analysis. On September 18, 2019, Transgene announced its decision to stop its Phase 1/2 trial evaluating Pexa-Vec in combination with nivolumab in this indication (first-line treatment of advanced liver cancer).
Transgene confirms that the first efficacy readouts from the trial evaluating TG4010 in combination with nivolumab and chemotherapy in the first-line treatment of lung cancer will be communicated during the course of December 2019.

Operating revenue

Revenue from collaborative and licensing agreements, amounted to €3.4 million in the first nine months of 2019, compared with €1.0 million in the same period in 2018. These revenues are mainly derived from the collaboration agreement with AstraZeneca on the Invir.IO program. An initial payment of €8.9 million ($10 million) was received in June 2019 and is recognized as income based on the progress of the activities associated with the collaboration until 2020. As of September 30, 2019, the income recognized was €2.5 million.

As of September 30, 2019, government financing for research expenditures mainly in the form of a research tax credit amounted to €4.5 million versus €4.3 million over the same period in 2018.

In the third quarter of 2018, Transgene saw a significant increase in operating revenues due to the sale of the Chinese rights of TG1050 to Tasly Biopharmaceuticals for €35.6 million ($41 million) in July 2018.

Cash, cash equivalents and other financial assets

Cash, cash equivalents, and other current financial assets stood at €53.9 million as of September 30, 2019, compared to €16.9 million as of December 31, 2018. This increase is due to the completion of a €48.7 million rights issue, that was settled on July 4, 2019. In the first nine months of 2019, Transgene’s cash burn was €10.1 million, excluding the net proceed from the rights issue, compared to €14.8 million for the same period in 2018.

Outlook

Transgene confirms that it expects to have a net cash burn target of approximately €20 million for 2019. Following the rights issue which completed in July 2019, Transgene has extended its financial visibility until 2022.

On November 14, 2019 Lipocine Inc. (NASDAQ: LPCN), a clinical-stage biopharmaceutical company focused on metabolic and endocrine disorders, reported the pricing of a public offering of (i) 10,450,000 Class A Units, each consisting of shares of its common stock and common warrants to purchase its common stock, and (ii) 1,550,000 Class B Units, each consisting of pre-funded warrants and warrants to purchase its common stock, at a price of $0.50 per Class A Unit and $0.4999 per Class B Unit (Press release, Lipocine, NOV 14, 2019, View Source [SID1234551332]). Gross proceeds to the Company are expected to be approximately $6.0 million, before deducting placement agent fees and other estimated offering expenses. The Company intends to use the net proceeds from this offering for working capital and general corporate purposes.

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Roth Capital Partners is acting as sole agent for the public offering.

The offering is being made pursuant to a shelf registration statement on Form S-3 (File No. 333-220942) (including a prospectus) previously filed with and declared effective by the U.S. Securities and Exchange Commission (the "SEC"). A prospectus supplement describing the terms of the offering will be filed with the SEC.

A copy of the final prospectus supplement and the accompanying prospectus relating to these securities may be obtained, when available, by contacting Roth Capital Partners, 888 San Clemente Drive, Suite 400, Newport Beach, CA 92660, (800) 678-9147. Electronic copies of the preliminary prospectus supplement and the accompanying prospectus will also be available free of charge on the website of the SEC at www.sec.gov.

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

On November 14, 2019 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines, reported third quarter 2019 financial results and provided an overview of operational progress (Press release, Rubius Therapeutics, NOV 14, 2019, View Source [SID1234551280]).

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"Over the last quarter, our team has successfully manufactured RTX-134 for our Phase 1b trial for the treatment of patients with phenylketonuria. Our clinical sites are actively recruiting patients, and we plan to announce when we have treated the first patient. In order for us to share follow up data from the first patients treated in the study, we expect to report initial clinical results during the first quarter of 2020," said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. "We continue to make good progress with our entire pipeline, having presented preclinical oncology data showcasing the versatility and potential power of the RED PLATFORM. We remain on track to file our first oncology Investigational New Drug application for RTX-240 by early 2020."

Recent Highlights and Upcoming Milestones

·Over the third quarter, Rubius Therapeutics successfully manufactured RTX-134 for our Phase 1b trial for the treatment patients with phenylketonuria (PKU).

·Rubius has clinical sites actively recruiting patients and plans to announce when the first patient has been treated.

· In order for Rubius to share follow up data from the first patients treated in the study, the Company expects to report initial clinical results during the first quarter of 2020, including:

·Preliminary safety;

· Longevity of RTX-134 in circulation; and

· Proof-of-mechanism as measured by production of trans-cinnamic acid, a metabolite of phenylalanine when degraded by phenylalanine ammonia lyase, or PAL.

·On November 8, 2019, Rubius presented preclinical data at the SITC (Free SITC Whitepaper) Annual Meeting, supporting its lead artificial antigen presenting cell program, RTX-321, for the treatment of HPV 16-positive tumors.

· RTX-321 is an allogeneic artificial antigen presenting cell engineered to express, on the cell surface, an HPV peptide antigen, 4-1BBL and IL-12 to mimic human T cell-APC interactions. RTX-321 is currently in IND-enabling studies.

·Proof-of-concept data generated in a B16-F10 melanoma mouse model demonstrated successful engineering of artificial antigen presenting cells against a melanoma tumor-associated antigen, gp100, that significantly expanded antigen-specific T cells and eliminated lung metastases with limited, reversible toxicity.

·On October 29, 2019, Rubius Therapeutics was issued U.S. Patent No. 10,456,421 covering Red Cell Therapeutic (RCT) compositions comprising 4-1BBL and their use for the treatment of cancer. 4-1BBL is expressed on the cell surface of each of the Company’s lead oncology product candidates: RTX-240, RTX-224 and RTX-321.

·Today, in total, Rubius Therapeutics has nine issued U.S. patents, including five composition of matter patents, 32 patent families and more than 150 pending patent applications worldwide.

·On October 27, 2019, Rubius Therapeutics presented preclinical data at the AACR (Free AACR Whitepaper)-NCI-EORTC, demonstrating the ability to engineer RCTs to create loadable artificial antigen presenting cells for personal neoantigens.

RTX-aAPCs with peptide-loaded MHC constructs functionally engaged TCRs and achieved robust expansion of primary cytomegalovirus (CMV)-specific T cells in healthy donor PBMCs with prior exposure to CMV.

Rubius Therapeutics’ loadable aAPC system has the potential to generate aAPCs containing multiple neoantigens in a single therapeutic.

·The Company continued to strengthen its leadership team by appointing Maiken Keson-Brookes as chief legal officer and corporate secretary.

Third Quarter Financial Results

Net loss for the third quarter of 2019 was $47.0 million or $0.59 per common share, compared to $26.4 million or $0.42 per common share in the third quarter of 2018.

In the third quarter of 2019, Rubius invested $33.5 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $14.4 million in the third quarter of 2018. This year-over-year increase was driven primarily by $8.6 million in incremental R&D program spending in preparation for the Company’s Phase 1b clinical trial for RTX-134 and towards preclinical activities for Rubius’ lead oncology programs, including RTX-240. In addition, $7.8 million in incremental R&D spending was driven by increased R&D headcount, a move into larger facilities and purchasing lab supplies to support Rubius’ goal of delivering four to five INDs across 2019 and 2020. Contract research costs increased by $1.9 million and R&D stock-based compensation also increased by $0.8 million.

G&A expenses were $15.0 million during the second quarter of 2019, as compared to $13.2 million for the third quarter of 2018. The higher costs were primarily driven by a $2.1 million increase in personnel and facility costs due to increased headcount in the general and administrative function, as well as increases in professional fees and infrastructure costs to support the Company’s growth.

Nine Month Financial Results

Net loss for the first nine months of 2019 was $119.0 million or $1.52 per common share, compared to $62.0 million or $2.33 per common share in the first nine months of 2018.

In the nine months ended September 30, 2019, Rubius invested $81.9 million in R&D related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $35.2 million in the first nine months of 2018. This year-over-year increase was largely due to an additional $22.4 million in R&D personnel, external research and facilities and lab supplies to support the Company’s pipeline expansion in 2019 and 2020 and $19.8 million in R&D program spending, including preparing for the RTX-134 Phase 1b clinical trial and preclinical activities for Rubius’ lead oncology programs, including RTX-240. R&D stock-based compensation also increased by $4.5 million.

G&A expenses were $42.3 million during the first nine months of 2019, as compared to $27.3 million for the same period in 2018. The higher costs were primarily driven by a $7.6 million increase in stock-based compensation and a $7.4 million increase in personnel costs and facility costs due to increased headcount in our general and administrative function, as well as increases in professional fees and infrastructure costs to support the Company’s growth.

Cash Position

As of September 30, 2019, cash, cash equivalents and investments were $324.7 million as compared to $404.1 million as of December 31, 2018, providing Rubius with a cash runway into 2021. During the year, the Company used $81.5 million of cash to fund operations and $27.4 million to fund capital expenditures, including work related to the buildout of Rubius’ manufacturing facility. In addition, during the year, the Company drew down a second tranche of $25.0 million from its $75.0 million loan agreement with Solar Capital in June 2019, which leaves a third tranche of $25.0 million that can be drawn through June 2020, subject to the satisfaction of certain financial covenants.

On November 14 , 2019 Aadi Bioscience, Inc. (Aadi), a privately held clinical stage biopharmaceutical company, reported its independent radiology reviewed data from the nab-sirolimus (ABI-009) registration trial (AMPECT) for Advanced (metastatic or locally advanced) Malignant PEComa (perivascular epithelioid cell tumor) – a rare form of sarcoma for which there is no currently approved therapy (Press release, Aadi, NOV 14, 2019, View Source [SID1234551313]).

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Nanoparticle albumin-bound sirolimus (nab-Sirolimus), an mTOR inhibitor, received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) in Dec 2018, "for the treatment of patients with advanced (metastatic or locally advanced) malignant perivascular epithelioid cell tumor (PEComa)."

The AMPECT trial was conducted at 9 U.S. sites and treated 34 adult patients, with 31 confirmed as PEComa by a central pathology laboratory. PEComa origin sites in these patients included the uterus, pelvis, retroperitoneum, lung, kidney, liver, brain, muscle, ovary, aorta, and small bowel.

Results of the primary analysis were released in an oral presentation (abstract 3206452) at the CTOS 2019 annual meeting in Tokyo, Japan, demonstrating a 39% confirmed independent radiology reviewed objective response rate (ORR) in patients with advanced PEComas originating in various tissues. Responses were rapid and durable with half the responders having an ongoing response duration of 15.3 months or longer and the majority of responders (67%) are still on treatment. AMPECT Investigator and lead author on the oral presentation, Mark Dickson, M.D., from Memorial Sloan Kettering Cancer Center, said "nab-sirolimus delivered highly durable responses in advanced PEComa patients. Most of the responding patients achieved a response by their first assessment at 6 weeks following initiation of therapy and these patients have stayed on therapy for extended periods with a manageable safety profile. We are encouraged by the outcomes in this first-ever prospective clinical trial in advanced PEComa." A second presentation by the principal investigator of the AMPECT trial, Dr Andrew Wagner M.D., Ph.D., from the Dana-Farber Cancer Institute, highlighted the exploratory mutational analysis from the study (abstract 3258096). "Patients having mutations in the TSC2 gene were found to have an 89% confirmed response rate to nab-sirolimus, while patients with TSC1 mutations or no mutations in the TSC1 or TSC2 genes had lower response rates. This is the first prospective study of outcomes vs mutational status of mTOR pathway genes and highlights the relevance of TSC2 mutations in advanced PEComa," Dr. Wagner said.

Neil Desai, Ph.D., Chief Executive Officer of Aadi Bioscience, said "The Aadi Bioscience team is grateful to the patients, families, and clinical trial teams who help expand the boundaries of available care through their participation in clinical trials. These results are an important milestone in the ongoing development of nab-sirolimus across a wide range of diseases and therapeutic indications that are driven by mTOR activation and for which there is a need for new therapies." Dr. Desai added: "Results from the AMPECT study will serve as the basis for the New Drug Application (NDA) for nab-sirolimus, which the company expects to submit to the FDA in the first half of 2020."

Key Data Presented at CTOS

The primary endpoint for the AMPECT study presented at CTOS is independent central radiology reviewed ORR, assessed by RECIST v 1.1. Key secondary endpoints include duration of response (DOR), progression-free survival (PFS), PFS rate at 6 months (PFS6), and safety. The data presented at CTOS represent a May 22, 2019 data cut-off for the primary analysis, with an additional 5.5 months of follow-up (Nov 6, 2019) for the duration of response endpoint.

The data presented are based on 34 patients evaluable for safety and 31 patients evaluable for efficacy per defined criteria in the protocol.

Best Response Assessment

Ninety percent of patients had a best response PR or SD, with disease control (defined as a confirmed response + SD ≥12 weeks) achieved in 71% of patients.

As of Nov 6, 2019, 75% (9/12) of responders had been on therapy for more than 1 year and 42% (5/12) for more than 2 years, with 67% (8/12) still on treatment. Median DOR has not been reached (range [5.6 –33.2+ months]) and 50% of the responders have a response duration that is 15.3 months or longer; the median time to response was 1.4 months (95% CI: 1.3, 2.7).

Median PFS is 8.9 months (95% CI: 5.5, –), PFS rate at 3 months (PFS3) is 79%, PFS6 is 70%, and 26% (9/34) of all patients enrolled remain on treatment. For reference, per a meta-analysis of 10 years of phase 2 trials in advanced soft tissue sarcomas (STS) published by the EORTC STS and Bone Sarcoma Group [2], the PFS3 and PFS6 are widely accepted as a meaningful measure of activity of drugs in STS and may be utilized to determine acceptable criteria of benefit. Drugs yielding a PFS rate of ≥40% at 3 months and ≥14% at 6 months are considered to be ‘potentially active’ in advanced STS [1].

A protocol prespecified exploratory mutational and biomarker analysis was available for 25 patients on the AMPECT trial. Mutational status of the suspect genes TSC1 or TSC2 in the mTOR pathway were analyzed for association with patient response outcomes. Mutation or deletion of TSC1 or TSC2 (no overlap) occurred in 5 (20%) and 9 (36%) patients respectively, while 11 (44%) patients had no alterations in TSC1 or TSC2. Responses occurred in 9/9 (100%, 8 confirmed responses [89%], 1 unconfirmed response [11%]) patients with TSC2 mutations, 1/5 (20%) patients with TSC1 mutations and 1/11 (9%) of patients with no mutations in TSC1 or TSC2.

The safety data presented at CTOS was available for all 34 patients treated on the AMPECT trial. The most common treatment-related hematologic adverse events of any grades included anemia (47%) and thrombocytopenia (32%) and the most common nonhematologic treatment-related adverse events of any grades included mucositis (79%), rash (56%), fatigue (59%), nausea (47%), and diarrhea (38%). Most of these events were grade 1 and 2, were manageable with dose modifications and no grade 4 events were observed. Twelve patients (35%) required dose reductions due to adverse events. Two patients (6%) discontinued nab-sirolimus due to an adverse event. There were no new or unexpected toxicities not previously known for mTOR inhibitor class.

The AMPECT Phase 2 registration trial for Advanced Malignant Perivascular Epithelioid Cell Tumors completed enrollment in late 2018. Aadi previously received agreement from the FDA that this open label study in at least 30 efficacy evaluable patients with a primary endpoint of independently reviewed ORR, could support the submission of an NDA for approval to treat this rare disease assuming a 30% response rate was observed and the lower bound of the 95% confidence interval of the ORR exceeded 14.7%. These data have not been reviewed by any regulatory agencies.