On January 27, 2020 Santhera Pharmaceuticals (SIX: SANN) reported net revenues of CHF 27.9 million in 2019 from sales of Raxone for the treatment of Leber’s hereditary optic neuropathy (LHON), which was out-licensed to Chiesi Group from August 2019 (Press release, Santhera Pharmaceuticals, JAN 27, 2020, View Source [SID1234553587]). The Company made strong progress in advancing its lead neuromuscular compounds Puldysa (idebenone) and vamorolone towards market entry and regulatory submission, respectively.

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"We are pleased about Santhera’s strong progress in 2019 and are excited about the prospects 2020 holds," said Dario Eklund, CEO of Santhera. "Our late-stage neuromuscular assets targeting the high value Duchenne muscular dystrophy (DMD) market are nearing key inflection points. With Puldysa (idebenone), we anticipate offering the first drug for the treatment of respiratory dysfunction for non-ambulant DMD patients who are not taking glucocorticoids. Vamorolone, a first-in-class anti-inflammatory drug candidate shown in studies to improve muscle and motor function with a favorable clinical safety profile, is being developed to replace glucocorticoids as standard of care in ambulant DMD patients. We will continue working with clinical experts, patient advocacy groups and regulators in order to bring these promising treatments to patients with currently few alternative treatment options as soon as possible."

2019 Turnover

Net revenues CHF 27.9 million
Gross income of CHF 49.3 million from Raxone out-licensing agreement
Freely available liquid funds of CHF 31.4 million (December 31, 2019)
2019 full-year net revenues slightly above guidance
In 2019, Santhera reported net revenues of CHF 27.9 million (2018: CHF 31.7 million), slightly surpassing the Company’s full-year guidance. This includes sales of Raxone in the approved indication Leber’s hereditary optic neuropathy (LHON) in the first seven months of 2019. From August 2019, after the closing of the licensing transaction and the transfer of the Raxone-business to Chiesi Group, Santhera is commercializing Raxone for LHON in France in a transitional phase.

Upfront payment from Chiesi Group following closing of licensing agreement
In August 2019, Santhera recognized an initial gross income of CHF 49.3 million (EUR 44 million) from the licensing agreement with Chiesi Group. As previously announced per the agreement, Chiesi Group has in-licensed Raxone for LHON and all other ophthalmologic indications for all territories worldwide except the US and Canada for a total consideration of up to EUR 93 million.

As of December 31, 2019, freely available liquid funds (cash and cash equivalents) amounted to CHF 31.4 million (August 31, 2019: CHF 43.7 million). In addition, the Company held CHF 1.5 million of restricted cash designated for the interest payments related to the convertible bonds issued in 2017.

Pipeline and Regulatory Update

Anticipated near-term inflection points towards approval for both DMD pipeline candidates Puldysa (idebenone) and vamorolone are:

Q2-2020: CHMP opinion on marketing authorization application for Puldysa in DMD in Europe
Q4-2020: Launch of Puldysa in first European markets
Q4-2020: Read-out of topline data of pivotal trial for vamorolone in DMD
Q1-2021: Filing a New Drug Application for vamorolone in DMD in the US
Puldysa first launch in Europe in 2020 subject to positive opinion and approval from CHMP/EMA
The review of Santhera’s application for conditional marketing authorization (CMA) for Puldysa in the treatment of respiratory dysfunction in patients with DMD who are not using glucocorticoids is ongoing and the Company expects an opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) around mid-2020. Subject to a positive opinion and subsequent EU approval, Santhera expects to launch Puldysa in the first European markets in late 2020.

SIDEROS DMD trial enrollment with idebenone nearing completion
Patient enrollment in Santhera’s randomized, double-blind, placebo-controlled Phase 3 SIDEROS trial is expected to complete in Q2-2020 (clinicaltrials.gov: NCT02814019). With a study duration of 18 months, the last patient’s last visit is scheduled for Q4-2021. If positive, the study data will allow for regulatory submissions supporting the use of Puldysa in all DMD patients experiencing respiratory decline, irrespective of their glucocorticoid use, in Europe and the US.

Vamorolone pivotal VISION-DMD study progressing as cornerstone for US/European regulatory filings
ReveraGen BioPharma is currently enrolling the Phase 2b VISION-DMD study with vamorolone, designed as a pivotal efficacy and safety trial (VBP15-004; clinicaltrials.gov: NCT03439670). Read-out of topline 6-month data from the randomized placebo-controlled treatment period is expected by Q4-2020 followed by an NDA submission in the US by Q1-2021. Under the agreements between the parties and upon exercising its option, Santhera would receive the sub-license to ReveraGen’s vamorolone from Idorsia Ltd (SIX: IDIA) for all indications and all countries worldwide except Japan and South Korea. The marketing authorization application in Europe will require inclusion of 12-month data expected for Q2-2021.

Neuromuscular franchise a top priority for 2020
Santhera’s strategic priorities for 2020 are its neuromuscular franchise: Puldysa and vamorolone in DMD. For Puldysa, the focus is on the preparation for European market entry in DMD later in the year and the completion of enrollment into the SIDEROS trial to support planned regulatory submissions, particularly in the US. For vamorolone, the key milestone will be the VISION-DMD topline data readout, which if positive would allow for preparation of the NDA filing and pave the way for Santhera’s option exercise.

In parallel, the Company is advancing its clinical stage candidate POL6014 for cystic fibrosis and is evaluating further diversification of its platform type pipeline products, including development of additional indications in collaboration with partners.

Corporate Calendar

March 24, 2020 – Publication of the Annual Report 2019 (07h00 CET)
April 22, 2020 – Annual Shareholders’ Meeting

On January 27, 2020 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported the completion of the sale of its Priority Review Voucher (PRV) to an undisclosed buyer (Press release, Bavarian Nordic, JAN 27, 2020, View Source [SID1234553586]). Upon completion, the company received a cash consideration of USD 95 million.

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On January 27, 2020 Zymeworks Inc. (NYSE: ZYME), a clinical stage biopharmaceutical company developing multifunctional biotherapeutics ("Zymeworks" or the "Company"), reported the closing of its previously announced underwritten public offering (the "Offering") (Press release, Zymeworks, JAN 27, 2020, View Source [SID1234553579]). The Offering consisted of 5,824,729 common shares, including the exercise in full of the underwriters’ over-allotment option to purchase 900,000 additional shares, and, in lieu of common shares, to a certain investor, pre-funded warrants to purchase up to 1,075,271 common shares. The common shares were offered at a price to the public of US$46.50 per common share and the pre-funded warrants were offered at a price of US$46.4999 per pre-funded warrant, for aggregate gross proceeds to the Company of approximately US$320.8 million, before deducting underwriting discounts and commissions and estimated Offering expenses.

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The Company intends to use the net proceeds of the Offering (i) to accelerate and expand the global development of ZW25 both as a single agent and in combination with other anti-cancer agents in a variety of HER2-expressing tumors, including gastroesophageal, biliary tract, breast and other underserved cancers; (ii) to accelerate and expand the clinical development of ZW49; (iii) to advance other novel preclinical programs, including those involving non-HER2-expressing tumors; and (iv) for general corporate purposes.

J.P. Morgan Securities LLC and Citigroup Global Markets Canada Inc. acted as active bookrunners for the Offering. Stifel, Nicolaus & Company, Incorporated and Wells Fargo Securities Canada, Ltd. acted as bookrunners and Raymond James Ltd. acted as lead manager.

The securities described above were offered in Canada pursuant to Zymeworks’ final prospectus supplement, dated January 22, 2020 (the "Canadian Supplement"), to its Canadian final base shelf prospectus, dated November 18, 2019 (the "Base Prospectus"), and in the United States pursuant to Zymeworks’ final prospectus supplement, dated January 22, 2020 (the "U.S. Supplement", together with the Canadian Supplement, the "Supplements"), to its U.S. automatic shelf registration statement on Form S-3ASR, including a prospectus dated November 5, 2019 (the "Registration Statement"). The Supplements were filed in Canada and the United States on January 23, 2020.

The Supplements and the Registration Statement contain important detailed information about the Offering. A copy of the Canadian Supplement can be found on SEDAR at www.sedar.com, and a copy of the U.S. Supplement and the related Registration Statement can be found on EDGAR at www.sec.gov. Copies of the Supplements may also be obtained from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204; Citigroup Global Markets Canada Inc., Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (800) 831-9146; Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720, or by email at [email protected]; or Wells Fargo Securities Canada, Ltd., Attention: Equity Syndicate Department, 30 Hudson Yards, 500 West 33rd Street, New York, NY 10001, by telephone at (800) 326-5897, or by email at [email protected]. Prospective investors should read the Supplements and the Registration Statement before making an investment decision.

This news 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 province, state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such province, state or jurisdiction.

On January 27, 2020 Zai Lab Limited ("Zai Lab" or the "Company") (NASDAQ: ZLAB), a China and U.S.-based innovative commercial stage biopharmaceutical company, reported the closing of its previously-announced underwritten public offering of 5,500,000 American depositary shares ("ADSs"), each representing one ordinary share of the Company (the "Primary ADS Offering"), at a price of US$47.50 per ADS (Press release, Zai Laboratory, JAN 27, 2020, View Source [SID1234553578]). In addition, QM11 Limited, a shareholder of the Company, offered 500,000 ADSs of the Company (the "Secondary ADS Offering" and together with the Primary ADS Offering, the "Offering") at the same price.

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Zai Lab and QM11 Limited had also granted the underwriters a 30-day option to purchase up to an additional 800,000 and 100,000 ADSs, respectively at the public offering price, less underwriting discounts and commissions. The underwriters fully exercised their option to purchase these additional ADSs. Given the full exercise of the option, QM11 Limited now owns approximately 12.15% of the Company’s share capital immediately following this Offering. The Offering closed on January 27, 2020.

The gross proceeds to Zai Lab from this Offering, before deducting underwriting discounts and commissions and other offering expenses, were approximately US$299.3 million. Zai Lab did not receive any proceeds from the sale of ADSs by QM11 Limited.

J.P. Morgan, Citigroup, Goldman Sachs & Co. LLC and SVB Leerink acted as joint book-running managers, and Guggenheim Securities acted as lead manager for the Offering.

The ADSs were offered pursuant to a shelf registration statement on Form F-3ASR, which became automatically effective upon filing with the U.S. Securities and Exchange Commission ("SEC") on March 29, 2019 and was subsequently amended and became automatically effective upon filing with the SEC on January 21, 2020.

The Offering was made only by means of a prospectus supplement and an accompanying prospectus included in Form-3ASR. The registration statement on Form F-3ASR and the prospectus supplement are available at the SEC’s website at: View Source Copies of the prospectus supplement and the accompanying prospectus may be obtained from: (i) J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at 1-866-803-9204 or by email at [email protected], (ii) Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by telephone at 1-800-831-9146, (iii) Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at 1-866-471-2526, by facsimile at (212) 902-9316 or by email at [email protected] or (iv) SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525 ex. 6132 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy ADSs or any other securities, nor shall there be any sale of ADSs 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 January 27, 2020 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, oncology therapeutics company targeting cancers that are both highly prevalent and in need of new effective treatment options including colorectal, prostate and acute myeloid leukemia, reported positive data from an ongoing Phase 1b/2 clinical trial of onvansertib plus FOLFIRI and Avastin (bevacizumab) for second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Trovagene, JAN 27, 2020, View Source [SID1234553577]).
The data demonstrate the pan-KRAS inhibitory effect of onvansertib. All five patients evaluable for efficacy assessment have shown a significant reduction in their KRAS mutational burden as measured by a simple blood test, which was subsequently confirmed by tumor regression visible on radiographic scans. Three patients had a >25% tumor shrinkage and one patient is now eligible for curative surgery, a clinically meaningful achievement, which is considered to be unprecedented in this patient population with only a 5% response to standard-of-care. The data was featured in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) in San Francisco on Saturday, January 25th, 2020.
Onvansertib is an oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor and may provide an answer to effectively "drugging" the once thought-to-be "undruggable" KRAS mutation. PLK1 has been identified as having synthetic lethality, which means that KRAS-mutated tumors have a higher sensitivity to PLK1 inhibition compared with KRAS wild-type cells.

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"Early results from the onvansertib Phase 1b/2 trial are very exciting and encouraging," said Dr. Daniel Ahn, the principal investigator at the Mayo Clinic Cancer Center. "Regardless of the specific KRAS mutation, we are seeing decreases in the mutational burden and tumor regression in all of our patients. This is indicative of onvansertib’s effect as a pan-KRAS inhibitor."
"Successfully treating patients in the second-line setting has been quite challenging to-date, with a relatively low response rate and poor prognosis," said another of the trial’s investigators, Dr. Tanios Bekaii-Saab, leader of the Gastrointestinal Cancer Program at the Mayo Clinic Cancer Center. "The combination of onvansertib plus standard-of-care FOLFIRI/bevacizumab offers promise as being both safe and effective."

Trovagene Inc. | 11055 Flintkote Avenue | San Diego | CA 92121 | Tel.: USA [+1] 888-391-7992

KRAS, which controls cell proliferation, has long been recognized as a major oncogene, responsible for many cancer types. Approximately 50% of mCRC patients have the KRAS mutation. The efficacy of current second-line therapy in terms of survival prolongation and response remains very limited, especially in this population, where there is only a 5% response rate. The other KRAS contenders including Amgen and Mirati, have produced some potentially promising early clinical results in non-small cell lung cancer (NSCLC); however, their drug candidates have shown limited activity in CRC as they only address one specific KRAS mutation, G12C, which accounts for only 8% of CRC, leaving room for drug developer, Trovagene, and its drug candidate onvansertib.

Onvansertib KRAS-Mutated mCRC Trial Data Highlights:

In the Phase 1b dose escalation, the 1st dose level (onvansertib 12 mg/m2) was cleared for safety; the 2nd dose level (onvansertib 15 mg/m2) is fully enrolled with no DLTs reported in the two patients treated to-date

Radiographic scans performed at 8 weeks showed tumor decrease and clinical benefit in 100% (n=5) of evaluable patients treated with onvansertib 12 mg/m2 (n=5); 1 patient achieved PR, 4 patients achieved SD

Radiographic responses were confirmed at 16 weeks with further tumor shrinkage in all patients; 3 patients had a >25% decrease; 1 patient is proceeding to curative surgery

Five different KRAS mutant variants were detected in 6 patients, which represents >90% of KRAS mutations in CRC; all five KRAS variants decreased within the 1st cycle of treatment (onvansertib dose levels 12 and 15 mg/m2)

At dose level 1 (onvansertib 12 mg/m2), 4 patients had detectable KRAS mutant ctDNA at baseline; in all 4 patients KRAS was undetectable within the 1st cycle of treatment; this preceded subsequent tumor shrinkage observed with radiographic scans, supporting the predictive value of liquid biopsy

At dose level 2 (onvansertib 15 mg/m2), the 2 patients treated to-date had detectable KRAS mutant ctDNA at baseline; in 1 patient KRAS was undetectable within the 1st cycle of treatment; radiographic scans will be performed at 8 weeks
About the Phase 1b/2 Clinical Trial of Onvansertib in KRAS-Mutated mCRC
The ongoing trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410) is evaluating the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed or are intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and the Mayo Clinic Cancer Center.
About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a

24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along
with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.
Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410; and a Phase 2 clinical trial of onvansertib in combination with decitabine in patients with relapsed or refractory AML (NCT03303339).
Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.