Arrowhead Pharmaceuticals Announces Pricing of Underwritten Public Offering of Common Stock

On December 4, 2019 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported the pricing of an underwritten public offering of 4,000,000 shares of its common stock, offered at a price of $58.00 per share, before underwriting discounts (Press release, Arrowhead Pharmaceuticals, DEC 4, 2019, View Source [SID1234551925]). The offering is expected to close on or about December 6, 2019, subject to customary closing conditions. In addition, Arrowhead has granted the underwriters of the offering a 30-day option to purchase up to an additional 600,000 shares of common stock at the public offering price, less the underwriting discount. Gross offering proceeds will be approximately $232 million, before deducting underwriting discounts and commissions and offering expenses.

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Goldman Sachs & Co. LLC, Jefferies LLC and Piper Jaffray & Co. are acting as bookrunning managers for the offering, Cantor Fitzgerald & Co. is acting as passive joint bookrunner for the offering and Robert W. Baird & Co. Incorporated and B. Riley FBR, Inc. are acting as co-managers for the offering. Arrowhead intends to use the net proceeds from this offering for general corporate purposes, including working capital, capital expenditures, research and development expenditures and clinical trial expenditures. A portion of the net proceeds may also be used for the acquisition of complementary businesses, products and technologies, or for other strategic purposes.

A shelf registration statement on Form S-3 (File No. 333-235324) relating to the public offering of the shares of common stock described above was filed with the Securities and Exchange Commission (the "SEC") and became automatically effective upon filing on December 2, 2019. A final prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s web site at www.sec.gov. When available, copies of the final prospectus supplement may also be obtained from Goldman Sachs & Co. LLC by mail at 200 West Street, New York, NY 10282, Attention: Prospectus Department, by telephone at (866) 471-2526, or by email at [email protected]; from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; or from Piper Jaffray & Co., Attn: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924, or by email at [email protected].

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 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.

Trovagene Announces Data Showing Ability of Onvansertib to Rescue Venetoclax-Resistance in Acute Myeloid Leukemia (AML)

On December 4, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis), for the treatment of various cancers including leukemia, prostate and colorectal, reported new in-vitro and in-vivo data suggesting that onvansertib may provide a new therapeutic option for patients who develop resistance to frontline treatment with venetoclax (Press release, Trovagene, DEC 4, 2019, View Source [SID1234551924]).

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The data show that onvansertib, as a single agent, inhibits tumor growth in venetoclax (Venclexta – Abbvie) resistant in-vitro and in-vivo models. Additionally, the data also demonstrate synergy with the combination of onvansertib and venetoclax, providing further support for the ability of onvansertib to rescue patients once they show signs of resistance to venetoclax. Currently, there are no viable treatment options for patients once they develop resistance to venetoclax; the median overall survival is only 1.7 to 2.3 months and prognosis is poor. Onvansertib represents a new therapeutic option to treat venetoclax-resistant AML and potentially increase progression-free and overall survival for these patients.

"We are very encouraged by the data suggesting that onvansertib will be able to rescue AML patients once they develop resistance to frontline treatment with venetoclax," said Dr. Mark Erlander, Chief Scientific Officer of Trovagene. "In our current Phase 2 AML trial, we are targeting venetoclax-resistant patients and treating them with the combination of onvansertib plus hypomethylating agent decitabine. We are also considering plans to conduct a future clinical trial of onvansertib in combination with venetoclax in patients showing initial signs of resistance to venetoclax to provide a new therapeutic option in an indication with significant clinical need."

AML is the most common acute leukemia in adults and is most frequently diagnosed in those 65 to 74 years of age. Prognosis is generally poor and worsens with advanced age. Current first-line treatment options for AML include induction chemotherapy; however, many older patients are not candidates for this treatment option. With the introduction of venetoclax, the treatment landscape has evolved and elderly patients who are not eligible for intensive chemotherapy are receiving venetoclax in combination with a hypomethylating agent frontline. Resistance tends to develop within approximately 11 months following initiation of treatment with venetoclax and today there are no viable therapies for these patients and their prognosis is poor. Thus, there is a significant medical need for new therapeutic options to treat patients once they develop resistance to venetoclax.
About the Ongoing Phase 2 Clinical Trial of Onvansertib in AML

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

The ongoing multi-center open label Phase 2 AML trial (NCT03303339) of onvansertib in combination with decitabine will enroll a total of 32 patients. Eligible patients are either treatment naïve and not candidates for induction therapy or have relapsed/refractory disease following treatment with one prior regimen, including patients treated with venetoclax in combination with a hypomethylating agent. Patients will receive onvansertib, administered orally, on days 1 through 5 of each 21-28-day cycle in combination with decitabine. The primary efficacy endpoint of objective response (CR + CRi) will be assessed in patients who complete at least 1 cycle of treatment.

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 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

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.

Sesen Bio Completes Successful CMC Type B pre-BLA Meeting with FDA

On December 4, 2019 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported the successful completion of a constructive Type B pre-BLA meeting with the FDA regarding the final Chemistry, Manufacturing and Controls (CMC) content of the Company’s Biologics License Application (BLA) for Vicinium (Press release, Sesen Bio, DEC 4, 2019, View Source [SID1234551923]). As previously announced, the Company expects to initiate the submission of the BLA for Vicinium in December 2019.

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"After four highly collaborative and productive meetings with the FDA in 2019, we feel increasingly confident in the regulatory path forward for Vicinium," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio.

Sesen Bio reached agreement with the FDA on the final content of the BLA and no further meetings were requested by the FDA at this time. The Company also gained a clear understanding of the FDA’s requirements for the process performance qualification (PPQ) campaign for bulk drug substance and drug product manufacturing. In addition, the Company continues to work in partnership with the FDA to accelerate the timing of the Pre-License Inspection (PLI) of the drug substance manufacturer, which is anticipated to expedite review of the BLA.

Additional details on regulatory progress in support of the potential approval of Vicinium are expected to be announced this December.

Key December 2019 Events

Anticipated initiation of BLA submission under a Rolling Review
Sesen Bio Regulatory Update
About Vicinium
Vicinium, a locally-administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicinium is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA trial, designed to support the registration of Vicinium for the treatment of high-risk NMIBC in patients who have previously received a minimum of two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicinium promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

SELLAS to Present at the 12th Annual LD Micro Main Event

On December 4, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported Angelos Stergiou, M.D., ScD h.c., President and Chief Executive Officer of SELLAS, will present a corporate overview at the 12th Annual LD Micro Main Event on Wednesday, December 11, 2019 at 9:00 a.m. PT in Los Angeles, CA (Press release, Sellas Life Sciences, DEC 4, 2019, View Source [SID1234551922]).

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A live audio webcast of the presentation will be available under "Events & Presentations" in the Investors section of SELLAS’ website at www.sellaslifesciences.com/investors. A replay of the webcast will be available for up to 30 days on SELLAS’ website following the presentation.

Moleculin Announces Additional Positive Interim Results from Phase 1/2 Clinical Studies of Annamycin in Acute Myeloid Leukemia

On December 4, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported additional positive interim safety and efficacy data from one of the Company’s two ongoing open label, single arm Phase 1/2 studies of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia ("AML") (Press release, Moleculin, DEC 4, 2019, View Source [SID1234551921]).

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The Phase 1 portion of these clinical trials, which are described in more detail later in this press release, is designed to establish the safety of Annamycin and to determine the Recommended Phase 2 Dose to be used in the Phase 2 portion of the trials. While the Primary Endpoint of the Phase 1 portion is safety, a Secondary Endpoint is the assessment of efficacy generally defined as an improvement in bone marrow biopsy results sufficient to qualify patients for a potentially curative bone marrow transplant. The Company cautions not to place undue reliance on interim results.

The third cohort in Poland receiving a single dose of 180 mg/m2 in the Phase 1 dose escalation portion of the trial was completed with no adverse events and the trial will continue to the next cohort of 210 mg/m2. In the US trial, one patient has completed treatment in the second cohort at 120 mg/m2. This brings the total number of patients treated and evaluated at or above 120 mg/m2 to 10. An additional patient in the US has begun treatment at 120 mg/m2 but has yet to complete post-treatment evaluation. The interim results for these 10 patients are 1 CRi (defined as a complete response with incomplete recovery of white blood cells and/or platelets) and 2 partial responses ("PRs" or where bone marrow blasts are reduced 50% and to below 25%). One additional patient was bridged to bone marrow transplant ("BT") based on a sufficient reduction in bone marrow blasts, bringing the total to 4 out of 10 patients at or above 120 mg/m2 who have demonstrated efficacy.

In the latest cohort in Poland, 1 of the 3 patients treated at 180 mg/m2 had a PR sufficient to qualify for a potentially curative bone marrow transplant. The results for all 3 patients were reviewed by the Safety Review Committee, which determined that no drug-related adverse events were observed that would prevent advancing the trial to the next higher dose level of 210 mg/m2. To date in the European trial, only one adverse event related to Annamycin has been reported; a patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days). In the Company’s parallel US clinical trial, one new patient (the first of cohort #2) achieved a "morphologically leukemia free state" or MLFS, which also constitutes a CRi, after receiving a single dose of 120 mg/m2.

We refer to Annamycin as a "next generation anthracycline," because it is designed to provide enhanced therapeutic benefits when compared with traditional anthracyclines (like doxorubicin) while reducing the potential for unwanted cardiotoxicity, or damage to the heart. This design intent has previously been validated with preclinical toxicology studies in animal models (as required by FDA) demonstrating Annamycin has little to no cardiotoxicity when compared with doxorubicin. Of the 14 patients treated thus far in both trials, none has shown any evidence of cardiotoxicity. This includes 7 patients in Poland who were treated at levels above the US maximum allowable cumulative anthracycline dose level (550 mg/m2), a limitation not imposed on our trial in Europe. If upheld in further studies, this lack of toxicity could be an important differentiator between Annamycin and the currently approved anthracyclines, for which cardiotoxicity is a well-known treatment limitation.

For example, a recent review published in Cardiovascular Drugs and Therapy (View Source) reported that 65% of patients who received the equivalent of 550 mg/m2 of doxorubicin (a current standard of care anthracycline) exhibited sub-clinical cardiotoxicity, defined as a reduction in left ventricular ejection fraction >10% points to a value <50%. Of the 5 patients mentioned above who were treated in our European trial above 550 mg/m2, no evidence of cardiotoxicity was detected. The same published review also suggested that a better long-term indicator of cardiotoxicity may be the measurement of an increase in a biomarker called Troponin. When measured as an early biomarker of cancer therapy-related cardiotoxicity, Troponin rise occurs consistently in 21% – 40% of patients after treatment with current standard of care anthracycline chemotherapy and, per the published review, such an increase in Troponin is associated with an increased risk of heart disease later in life. Of the 14 patients treated thus far in both of our Annamycin clinical trials, none has shown an increase in Troponin levels.

"The interim data from our early-stage clinical trials of Annamycin continues to meet or exceed our expectations, from both a safety and efficacy perspective," commented Walter Klemp, Moleculin’s Chairman and CEO. "We believe the activity we are seeing – with 40% of patients treated at or above 120 mg/m2 responding with CRi’s, PR’s and/or bridging to a potentially curative bone marrow transplant – is encouraging, especially since we have yet to reach a maximum tolerable dose. Although the data is preliminary, we are excited by the results to date, and to continue moving forward. Importantly, recruitment continues to be much faster in Europe than in the US. We believe this is because Europe has imposed fewer regulatory constraints on the level of anthracycline dosing allowed and because there are far fewer competing AML clinical trials in Poland, where our clinical testing sites are located."

"We should also point out," Mr. Klemp continued, "that there are two particularly important aspects of our development program that distinguish the potential prospects for Annamycin. First, we are studying the potential benefits of Annamycin in all AML patients, not just a subset of the AML population based on a particular gene mutation or other biomarker. Second, Annamycin is being investigated not as an adjuvant to other therapies, but as a single agent to treat relapsed or refractory AML patients, primarily as a bridge to transplant. We also believe the absence of cardiotoxicity, if it is borne out, would be especially important for pediatric patients, in addition to possibly suggesting Annamycin as an attractive alternative to currently approved anthracyclines for treating cancers beyond AML."

Dr. Robert Shepard, Moleculin’s Chief Medical Officer for Annamycin added: "Although it is still early and the data are preliminary, I believe we may see that Annamycin has significant activity against relapsed and refractory AML. To have a 40% response rate this early in the dose-escalating process is very encouraging. And if the product ultimately is shown to have little or no cardiotoxicity – as the preliminary data suggest – there is a real potential for Annamycin to become the first approved anthracycline without a dose-limiting cardiovascular risk. The use of anthracyclines for induction therapy in acute leukemia is often, and unfortunately, limited if such treatment would put them over what is currently considered the ‘lifetime maximum’ anthracycline exposure (or ‘maximum cumulative dose’). However, authorities in the EU took into account Annamycin’s apparent lack of cardiotoxicity and have allowed us to demonstrate this in patients whose treatment would exceed this maximum cumulative dose. In fact, 7 of the 9 patients treated to date in Europe substantially exceeded that lifetime maximum based on their treatment with Annamycin and, of course, have shown no cardiotoxicity."

Study Design

The Company is studying Annamycin in both the US and Europe in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. The US and European trials have the same study design, consisting of a Phase 1 intended to establish a "Recommended Phase 2 Dose" ("RP2D"), to which the studies will then proceed. The Phase 1 studies provide for escalating doses in cohorts of 3 patients each, with each successive cohort receiving the next higher dose level until "dose limiting toxicities" prevent further increases. Cohorts 1, 2 and 3 in Poland received a dose of 120, 150 and 180 mg/m2, respectively, and the results now permit moving to 210 mg/m2. Cohort 1 in the US started at 100 mg/m2, and the results supported moving to 120 mg/m2, at which 1 patient has now been treated and evaluated as having achieved a "morphologically leukemia free state" or MLFS, which also constitutes a CRi. Because one patient in US cohort 1 did not complete the evaluation protocol, a fourth patient was added to complete that cohort. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

The data reported here is preliminary as collected by independent CRO site monitors per standard practice and is subject to subsequent quality assurance review.

We have been and intend to continue reporting top-line results by cohort in each trial, with each announcement also including an update on the other trial. Top-line results will include reporting of any drug-related adverse events ("AEs") and assessment of cardiotoxicity, including ECHO or MUGA scans measuring change in ejection fraction and measuring blood Troponin level, which is considered a biomarker for potential long-term cardiovascular impairment. To date, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other drug-related AEs have been reported. Also, no loss of ejection fraction or rise in Troponin levels has been reported. Top-line results will also include the number of partial responses ("PRs"), complete responses ("CRs") and patients deemed capable of progressing to a potentially curative bone marrow transplant, which we term "bridge to transplant" ("BTs"), each of which is essentially a function of the magnitude of reduction in a patient’s bone marrow blasts. For purposes of these clinical trials, a CR means that the patient’s bone marrow blasts reduced to 5% or less (with CRi meaning a CR where there was incomplete recovery of white blood cell and/or platelet counts), a PR means the patient’s bone marrow blasts reduced by 50% and resulted in a blast count of 25% or less, and a BT means patients are deemed capable of progressing to a potentially curative bone marrow transplant. To date, there has been 1 CRi in the US (@ 120 mg/m2), 2 PRs in Europe (1 @ 120 mg/m2 and 1 @ 180 mg/m2) and 4 BTs (1 in the US and 3 in Europe).

The US trial also differs from the European trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2, as exceeding this dose level would require the patient to exceed the established lifetime maximum exposure to anthracyclines (presuming all anthracyclines are cardiotoxic). To date, 100% of all 14 patients treated in both the US and EU trials have shown no incidence of cardiotoxicity, including 7 patients out of 9 treated in Poland who exceeded the lifetime maximum anthracycline exposure level. The Company believes that the additional

patient safety data gained from the European trial may also assist in the FDA’s review of Annamycin’s cardiac safety.