On March 12, 2020 BridgeBio Pharma, Inc. (Nasdaq: BBIO) affiliate company QED Therapeutics reported that patients have been dosed in separate Phase 3 and Phase 2 clinical trials of infigratinib in cancer indications (Press release, BridgeBio, MAR 12, 2020, View Source [SID1234556926]).

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The Phase 3 PROOF 302 trial sponsored by QED is studying infigratinib for the adjuvant (post-surgery) treatment of invasive urothelial carcinoma. A second, investigator-initiated trial, led by Sameek Roychowdhury, M.D., Ph.D., of The Ohio State University (OSU) Comprehensive Cancer Center, is studying infigratinib for the treatment of advanced and metastatic solid tumors with confirmed FGFR gene fusions/translocations or other FGFR alterations.

In the PROOF 302 trial, investigators are enrolling subjects with invasive urothelial cancer harboring susceptible FGFR3 genetic alterations who are at high risk of recurrence following surgical resection. Subjects will be randomized (1:1) to receive once daily oral infigratinib or placebo. The primary outcome is disease-free survival, and secondary outcomes include metastasis-free survival, overall survival, and safety and tolerability measures.

"Many patients with invasive urothelial carcinoma will have their cancer recur within two years after surgery," said PROOF 302 trial lead Sumanta Pal, M.D., professor of medical oncology and therapeutics research at City of Hope Comprehensive Cancer Center. "Correspondingly, I believe there are many patients who could benefit from an oral, post-surgery treatment option that targets FGFR3 alterations, the genetic driver of many urothelial carcinomas."

The Phase 2 study at OSU and selected sites within the Oncology Research Information Exchange Network (ORIEN) will evaluate the efficacy of infigratinib in patients who have advanced or metastatic solid tumors that are positive for FGFR1-3 gene fusions/translocations or other FGFR alterations. The open-label study will assess overall response rate as the primary outcome. Secondary outcomes include progression-free survival, best overall response, disease control rate, overall survival and measures of safety and tolerability.

"Increasingly, oncologists are learning to classify their patients’ cancers based on genetic mutations, going beyond the origin of the tumor," noted Dr. Roychowdhury. "Given the activity we have seen with infigratinib in FGFR2-fusion-driven bile duct cancers and FGFR3-altered urothelial carcinoma, our hope is that infigratinib will demonstrate similar activity in additional cancers that appear to be driven by alterations in FGFR. There appear to be multiple FGFR alterations that can drive cancer growth—and we hope to see these patients benefit too."

For additional information on the PROOF 302 trial, including eligibility, patients should ask their physician, visit clinicaltrials.gov, or email [email protected].

For additional information on the Phase 2 trial in metastatic solid tumors with FGFR gene alterations, including eligibility, patients should ask their physician, visit clinicaltrials.gov, or email [email protected].

On March 12, 2020 The National Foundation for Cancer Research (NFCR)reported that it has recently been approved by the U.S. Food and Drug Administration (FDA) for the initiation of human clinical trials. The regulatory body accepted the Investigational New Drug (IND) application for ST-001, a unique intravenous (IV) nano-delivery system of the off-patent synthetic chemical compound fenretinide, for the experimental treatment of patients with T-cell non-Hodgkin’s lymphoma.

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Fenretinide is a small-molecule which past studies have shown to be both safe and have cancer mitigating qualities. However, heretofore it has not been approved as a cancer therapeutic, largely due to the challenges of delivering it in adequate doses to tumor cells.

The molecule is highly hydrophobic, meaning poorly soluble in water. Therefore, the clinical use of fenretinide as a cancer therapeutic by itself is limited—that is, unless delivered to cancer cells in a manner via which the molecule’s insolubility will no longer be problematic. Existing technology has not yet solved this problem.

However, funded in part by an NFCR grant, a unique nanoparticle-based IV delivery system has been developed which shows promise in being able to address the insolubility challenge and administer therapeutically effective high doses of fenretinide. Phase I clinical trials for its safety are expected to begin later this year at the Rush University Medical Center in Chicago.

NFCR’s translational research support helped advance the cancer treatment technology, developed by scientists including the U.S. National Cancer Institute’s Ralph Parchment, Ph.D., to this crucial IND acceptance stage. Additionally, optimism for the prospect of the upcoming trials’ successful outcome is justified by earlier research on fenretinide conducted and published by multiple scientists, including Dartmouth College’s Michael Sporn, M.D., a former NFCR project director, showing the drug to be safe in humans after long periods of use.

"The acceptance by the FDA of ST-001’s IND application underscores the importance of research—basic and translational—in the battle against not only lymphoma, but all forms of cancer," said NFCR President and CEO Sujuan Ba, Ph.D. "It’s only novel research that can result in game-changing treatments for patients."

On March 12, 2020 Merck & Co reported that the rejection, which would have been for adults who have had platinum-containing chemotherapy, comes after a review of new evidence collected while the MSD blockbuster was available via the Cancer Drugs Fund.

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NICE says that there is still uncertainty surrounding the long-term benefit of the second-line immunotherapy treatment in comparison with other options, meaning it is not a "cost-effective use of NHS resources at its current price."

The organisation says that the drug will be withdrawn from the Cancer Drugs Fund once final guidance has been published, meaning that no new patients will be offered the treatment, although it will not affect those whose treatment was started before the final guidance was published.

As it stands, the list price for Keytruda is £2,630 per 100mg vial, which would be given as 200mg intravenously every three weeks. Even when the drug is offered with its agreed discount, the most plausible cost-effectiveness estimate remains above what NICE normally considers acceptable, even for end-of-life treatments.

The rejection marks the second NICE ‘no’ for MSD and Keytruda in the last month or so, as the organisation released a draft guidance rejecting the drug in combo with Pfizer’s Inlyta (axitinib) to treat advanced renal cell carcinoma in February.

Urothelial cancer begins in the lining of the bladder and is thought to be caused by prolonged exposure to harmful substances such as those found in tobacco smoke. It is the most common form of bladder cancer and accounts for nine in 10 of all cases.

On March 12, 2020, Celsion Corporation (the "Company") reported that it has entered into private exchange agreements (the "Exchange Agreements") with certain holders (the "Investors") of warrants issued in connection with the Company’s registered direct offering of common stock and warrants (the "Original Warrants") issued on March 3, 2020 (Press release, Celsion, MAR 12, 2020, View Source [SID1234555549]). The Original Warrants being exchanged provided for the purchase of up to an aggregate of 2,971,428 shares of the Company’s common stock, par value $0.01 per share (the "Common Stock") at an exercise price of $1.15, with an expiration date of September 3, 2025.

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Pursuant to the Exchange Agreements, in return for a higher exercise price of $1.24 per share of Common Stock, the Company issued new warrants to the Investors to purchase up to 3,200,000 shares of Common Stock (the "Exchange Warrants") in exchange for the Original Warrants. The Exchange Warrants, like the Original Warrants, are initially exercisable six months following their issuance (the "Initial Exercise Date") and expire on the five year anniversary of the Initial Exercise Date. Other than having a higher exercise price, different issue date, Initial Exercise Date and expiration date, the terms of the Exchange Warrants are identical to those of the Original Warrants, additional terms of which are more fully described under Item 1.01 of the Company’s Current Report on Form 8-K filed on March 3, 2020, which such terms are incorporated herein by reference.

On March 12, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported pricing of a public offering of 20,000,000 units at a price to the public of $0.30 per unit, for gross proceeds of $6.0 million, before deducting placement agent fees and other offering expenses payable by Kitov (Press release, Kitov Pharmaceuticals , MAR 12, 2020, View Source [SID1234555545]). Each unit contains one American Depositary Shares ("ADS") (or ADS equivalent) and one warrant to purchase one ADS. Each ADS represents one ordinary share, no par value, of Kitov. The ADSs (or ADS equivalents) and warrants included in the units can only be purchased together in this offering, but will be issued separately and will be immediately separable upon issuance.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The warrants will have an exercise price of $0.325 per ADS and will be exercisable at any time after the date of issuance and will expire five years from the date of issuance.

The closing of the sale of the securities is expected to take place on or about March 16, 2020, subject to satisfaction of customary closing conditions.

Kitov intends to use the net proceeds of this offering to fund the development of its oncology drug candidates, acquisition of new assets and for general working capital purposes.

The offering is being made under an effective registration statement on Form F-1 (File No. 333-235729) filed with the Securities and Exchange Commission (the "SEC") and declared effective on March 11, 2020. The offering is being made only by means of a prospectus forming part of the effective registration statement. The final terms of the offering will be disclosed in a final prospectus to be filed with the SEC and made available on the SEC’s website at www.sec.gov. When available, electronic copies of the final prospectus relating to the offering may also be obtained by contacting H.C. Wainwright & Co., 430 Park Avenue, New York, NY 10022, by telephone at (646) 975-6996 or by email at [email protected]. This press release shall not constitute an offer to sell or a solicitation of an offer to buy nor shall there be any sale of these securities in any 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 state or jurisdiction.