On January 11, 2023 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases ("Can-Fite" or the "Company"), reported that it has entered into definitive agreements for the purchase and sale of 1,000,000 of the Company’s American Depositary Shares ("ADSs") (or ADS equivalents in lieu thereof), at a purchase price of $5.50 per ADS, in a registered direct offering (Press release, Can-Fite BioPharma, JAN 11, 2023, View Source [SID1234626186]). In a concurrent private placement, Can-Fite has also agreed to issue and sell 363,637 of its ADS (or ADS equivalents in lieu thereof), at the same purchase price as in the registered direct offering. In addition, the Company has agreed to issue in the offerings unregistered Series A warrants to purchase up to an aggregate of 1,363,637 ADSs and Series B warrants to purchase up to an aggregate of 1,363,637 ADSs. Each ADS represents three hundred (300) ordinary shares, par value NIS 0.25 per share, of Can-Fite. The offerings are expected to close on or about January 13, 2023, subject to satisfaction of customary closing conditions.

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

The Series A warrants will have an exercise price $6.00 per ADS, will become exercisable immediately upon issuance and have a term of five and one-half years from the date of issuance and the Series B warrants will have an exercise price $5.50 per ADS, will become exercisable immediately upon issuance and have a term of 20 months from the date of issuance.

The gross proceeds from the offerings (without taking into account any proceeds from any future exercises of warrants), before deducting the placement agent’s fees and other offering expenses payable by the Company, are expected to be approximately $7.5 million. Can-Fite intends to use the net proceeds for funding research and development and clinical trials and for other working capital and general corporate purposes.

The ADSs (or ADS equivalents) offered in the registered direct offering (but excluding the securities offered in the private placement and the ADSs underlying the warrants) are being offered and sold by Can-Fite pursuant to a "shelf" registration statement on Form F-3 (File No. 333-249063) originally filed with the U.S. Securities and Exchange Commission (the "SEC") on September 25, 2020 and declared effective by the SEC on October 9, 2020. The offering of the ADSs (or ADS equivalents) to be issued in the registered direct offering is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and the accompanying prospectus relating to the registered direct offering will be filed with the SEC. Electronic copies of the final prospectus supplement and the accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The securities issued in the private placement and the unregistered warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the ADSs underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the unregistered ADSs, the warrants and underlying ADSs may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

The Company also has agreed to amend certain warrants to purchase up to an aggregate of 600,000 ADSs of the Company that were issued in December 2021 by reducing the exercise prices from $20.00 per ADS to $5.50 pr ADS.

On January 11, 2023 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported pipeline and corporate updates at the 41st Annual J.P. Morgan Healthcare Conference (Press release, Precigen, JAN 11, 2023, View Source [SID1234626185]). Helen Sabzevari, PhD, President and CEO of Precigen, presented a summary of 2022 achievements and set forth Precigen’s goals for 2023.

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"Precigen continued to make significant clinical progress for our UltraCAR-T and AdenoVerse programs in 2022 and we were able to meet or exceed substantially all of the clinical goals we outlined at the J.P. Morgan Healthcare Conference last year. For example, the PRGN-2012 study in RRP continues to accelerate at a rapid pace and we look forward to hosting an R&D update call on January 24th to share safety and efficacy data from the Phase 1 dose escalation and expansion cohorts," said Helen Sabzevari, PhD, President and CEO of Precigen. "In 2023, we will continue to advance our clinical programs with a focus on a rapid path to licensure for programs addressing high unmet patient need."

PRGN-2012 AdenoVerse Immunotherapy in RRP

Overview: PRGN-2012 is an investigational off-the-shelf (OTS) AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with HPV 6 or HPV 11 for treatment of RRP. PRGN-2012 is currently under evaluation in a Phase 2 clinical trial (clinical trial identifier: NCT04724980). The clinical trial evaluates PRGN-2012 as an adjuvant immunotherapy following standard-of-care surgical removal of visible papillomas in adult patients with RRP. PRGN-2012 has been granted Orphan Drug Designation in patients with RRP by the US Food and Drug Administration (FDA).
Program Status: Enrollment (N=15) was completed in the Phase 1 study. Precigen initiated dosing in the Phase 2 trial and is rapidly enrolling patients, with 20 patients enrolled to date. The Company will host a virtual R&D event on January 24, 2023 to showcase complete clinical trial data from the Phase 1 dose escalation and expansion cohorts of PRGN-2012 AdenoVerse Immunotherapy in RRP. The event will be led by Clint T. Allen, MD, Senior Investigator, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute (NCI) and lead associate investigator for the PRGN-2012 clinical trial and Helen Sabzevari, PhD, President and CEO of Precigen. The Company plans to outline the regulatory strategy for PRGN-2012 in 2023 based on discussions with the FDA.
PRGN-2009 AdenoVerse Immunotherapy in HPV-associated Cancers

Overview: PRGN-2009 is an OTS investigational immunotherapy utilizing the AdenoVerse platform designed to activate the immune system to recognize and target HPV-positive (HPV+) solid tumors. PRGN-2009 is currently under evaluation in a Phase 1/2 clinical trial (clinical trial identifier: NCT04432597). The Phase 1 trial is evaluating safety and response of PRGN-2009 as a monotherapy (Arm A) and in combination with M7824 (Arm B) in previously treated patients with recurrent or metastatic HPV-associated cancers.
Program Status: Enrollment was completed in the Phase 1 monotherapy (N=6) and combination therapy (N=11) arms in patients with recurrent or metastatic HPV-associated cancers and patient follow up is ongoing. The Company expects Phase 1 monotherapy and combination therapy safety and efficacy data to be presented in the first half of 2023. Enrollment is nearing completion in the Phase 2 monotherapy arm in newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) patients with 19 of 20 estimated patients enrolled as of the end of 2022. Interim clinical data presentation from the Phase 2 monotherapy arm is expected in the second half of 2023.
PRGN-3006 UltraCAR-T in Acute Myeloid Leukemia (AML)

Overview: PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T cell (CAR-T) therapy engineered to simultaneously express a CAR specifically targeting CD33, membrane bound IL-15 (mbIL15), and a kill switch. PRGN-3006 UltraCAR-T is under evaluation in a Phase 1b clinical trial (clinical trial identifier: NCT03927261) for the treatment of patients with relapsed or refractory AML or higher-risk myelodysplastic syndromes (MDS). PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML and Fast Track Designation in patients with relapsed/refractory AML by the FDA.
Program Status: Enrollment was completed in the Phase 1 dose escalation cohorts of the study. Precigen presented positive Phase 1 dose escalation data for autologous PRGN-3006 UltraCAR-T manufactured overnight for next day infusion in relapsed or refractory AML patients at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The Phase 1b dose expansion study of PRGN-3006 UltraCAR-T was expanded to Mayo Clinic in Rochester, Minnesota, enhancing the decentralized manufacturing model. The first patient was successfully dosed at the expansion site with PRGN-3006 UltraCAR-T. Site activation activities are in progress at several additional major cancer centers across the US as part of the multicenter expansion of the study. The Company received FDA clearance to incorporate repeat dosing in the Phase 1b expansion phase of the study, at the discretion of the treating physician. Phase 1b clinical trial data presentation is expected in 2024.
PRGN-3005 UltraCAR-T in Ovarian Cancer

Overview: PRGN-3005 UltraCAR-T is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR specifically targeting the unshed portion of MUC16, which is highly expressed on ovarian tumors with limited normal tissue expression, mbIL15, and a kill switch. PRGN-3005 UltraCAR-T is under evaluation in a Phase 1b clinical trial (clinical trial identifier: NCT03907527) for the treatment of patients with advanced, recurrent platinum-resistant ovarian cancer.
Program Status: Enrollment was completed in the Phase 1 dose escalation cohorts of the intraperitoneal (IP) and intravenous (IV) arms without lymphodepletion as well as in the lymphodepletion cohort in the IV arm. Patient follow up is ongoing and the Company expects Phase 1 data to be presented in the first half of 2023. The first patient received a repeat PRGN-3005 dose via IV infusion, following FDA clearance to incorporate repeat dosing in the study protocol. Enrollment is ongoing in the Phase 1b expansion study of PRGN-3005 UltraCAR-T at Dose Level 3 with lymphodepletion prior to IV infusion. Site activation activities are in progress at multiple major cancer centers in the US. Phase 1b clinical trial data presentation is expected in 2024.
PRGN-3007 Next Generation UltraCAR-T with Intrinsic PD-1 Inhibition

Overview: PRGN-3007, based on the next generation of the UltraCAR-T platform, is an investigational multigenic, autologous CAR-T cell therapy engineered to simultaneously express a CAR targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), mbIL15, a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression. ROR1 is aberrantly expressed in multiple hematological tumors, including chronic lymphocytic leukemia (CLL), mantle cell leukemia (MCL), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL) and solid tumors, including breast adenocarcinomas such as triple negative breast cancer (TNBC), pancreatic cancer, ovarian cancer, and lung adenocarcinoma. ROR1 is minimally expressed in healthy adult tissues.
Program Status: Precigen presented an abstract titled, "A Phase1/1b Dose Escalation/Dose Expansion Study of PRGN-3007 UltraCAR-T Cells in Patients with Advanced Hematologic and Solid Tumor Malignancies," at ASH (Free ASH Whitepaper). Tech transfer was completed for initiation of the Phase 1 umbrella trial in ROR1+ hematological (CLL, MCL, ALL, DLBCL) and solid tumors (TNBC). The trial is currently open for enrollment and the Company expects to dose the first patient in the first quarter of 2023.

Precigen’s J.P. Morgan presentation is available on the Company website in the Events & Presentations section.

On January 11, 2023 Vivesto AB, an oncology-focused specialty pharmaceutical company, reported that Inceptua AB (a partner and sublicensee of Elevar Therapeutics Inc.), which holds the right to commercialize Apealea (paclitaxel micellar) in the European Union, UK and Switzerland, has decided that the market authorization application for Apealea, submitted to the Swiss Agency for Therapeutic Products (Swissmedic) on 15 November 2021, will be withdrawn (Press release, Vivesto, JAN 11, 2023, View Source [SID1234626184]).

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Swissmedic has concluded that based on current clinical data, a positive benefit-risk balance has not been proven for Apealea and has therefore indicated refusal of marketing authorization. There are currently no plans for further clinical development to accommodate approval in Switzerland for commercial reasons.

Apealea in combination with carboplatin is indicated for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer. The product is approved by the European Medicines Agency (EMA) and the Medicines & Healthcare products Regulatory Agency (MHRA) in the UK. Inceptua AB will continue the work to advance the commercial plans for Apealea.

On January 11, 2023 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported results from the first and largest post-commercial utilization review of JELMYTO (mitomycin) for pyelocalyceal solution (Press release, UroGen Pharma, JAN 11, 2023, https://investors.urogen.com/news-releases/news-release-details/results-first-post-commercial-utilization-review-jelmytor [SID1234626183]). This study evaluated 132 patients treated with JELMYTO from 15 high-volume academic and community centers and characterizes the manner in which urologists are now using JELMYTO in their practices. The study titled, "Early Experience with UGN-101 for the Treatment of Upper Tract Urothelial Cancer – A Multi-Center Evaluation of Practice Patterns and Outcomes," is published in Urologic Oncology: Seminars and Original Investigations.

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The authors describe several trends in JELMYTO use that differ from the pivotal Olympus study that led to drug approval. Doctors are using JELMYTO for the treatment of large tumors (>3cm in 15% of cases), high grade tumors (9% of cases), and ureteral tumors (35% of cases). In addition, the report documents the use of JELMYTO as a valuable multimodal adjunct following complete laser tumor ablation. JELMYTO is indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). Primary chemoablation resulted in a 70% complete response (CR) rate for patients with tumors less than 1cm (CR rates following primary therapy were lower for larger tumors consistent with previous reporting) while 69% achieved CR when JELMYTO was combined with laser ablation. CR in the Olympus trial was 59%.

Almost half of the patients in the review were treated by antegrade administration of JELMYTO through a nephrostomy tube. The Olympus cohort was treated exclusively by retrograde catheter passed into the upper tract through the bladder. The authors of a recent single-center retrospective review observed that antegrade administration of JELMYTO was associated with a lower rate of ureteric stenosis than the retrograde approach as observed in OLYMPUS, and this larger multi-center review supports that earlier observation. The rate of ureteric stenosis in the Olympus trial was 44%. In this multi-center study it was 23%.

The limitations of this study include the retrospective design, lack of a control group, the lack of a centralized pathology review, and standardized clinicopathologic assessment.

To further explore the full potential of JELMYTO for the treatment of patients with UTUC, investigators are in the process of enrolling the prospective and retrospective uTRACT Registry to capture data in a large scale, standardized manner to report further on patient outcomes following JELMYTO treatment including longitudinal follow-up.

"This study provides valuable insights into how physicians are utilizing JELMYTO in the real-world and reinforces the genuine clinical value of this therapy for patients with LG-UTUC," said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. "We look forward to additional analyses from this retrospective study as well as prospective and retrospective data from the uTRACT Patient Registry."

About UTUC
Approximately 5-7% of urothelial cancer occurs in the upper lining of the kidney, called the calyx and renal pelvis. It could also occur in one or both of the ureter(s), the tubes that lead from the kidneys to the bladder. Cancer in the renal pelvis or ureter(s) is called upper tract. LG-UTUC is usually not very aggressive and is slow to spread but has a high recurrence rate. High-grade UTUC can be more aggressive. It may spread to other parts of the urinary tract, or to other parts of the body.

JELMYTO is approved for the treatment of adults with LG-UTUC. LG-UTUC is a rare disease managed by endoscopic methods and radical nephroureterectomy. Endoscopic resection and laser ablation attempt to preserve the kidney, though there is a high risk of recurrence that may eventually necessitate removal of the kidney. Although kidney removal is the gold standard for treatment of high-grade UTUC, it may be over-treatment in LG-UTUC, as kidney removal offers similar five-year survival as kidney-sparing procedures but is associated with significant morbidity. JELMYTO is efficacious as a primary chemoablative therapy in patients with LG-UTUC.

About JELMYTO
JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for primary chemoablative treatment of LG-UTUC in adults. It is recommended for primary treatment of biopsy-proven LG-UTUC in patients deemed appropriate candidates for renal-sparing therapy. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

APPROVED USE FOR JELMYTO

JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC).

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.
are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain.

You are encouraged to report negative side effects of prescription drugs to the U.S. Food and Drug Administration. Visit www.fda.gov/medwatch or call 1800FDA1088. You may also report side effects to UroGen Pharma at 1-855-987-6436.

On January 11, 2023 Pulmatrix presented its corporate presentation (Presentation, Pulmatrix, JAN 11, 2023, View Source [SID1234626182]).

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