On June 8, 2023 Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) reported the pricing of $500.0 million aggregate principal amount of 1.75% Convertible Senior Notes due 2028 (the "notes") in a private placement (the "offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Ionis Pharmaceuticals, JUN 8, 2023, View Source [SID1234632661]). Ionis also granted the initial purchasers of the notes an option to purchase, within the 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $75.0 million aggregate principal amount of notes from Ionis. The sale of the notes is expected to close on June 12, 2023, subject to customary closing conditions.

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The notes will be general unsecured obligations of Ionis, and will accrue interest payable semiannually in arrears on June 15 and December 15 of each year, beginning on December 15, 2023, at a rate of 1.75% per year. The notes will mature on June 15, 2028, unless earlier converted or repurchased.

Ionis estimates that the net proceeds from the offering will be approximately $487.6 million (or approximately $560.8 million if the initial purchasers exercise their option to purchase additional notes in full), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses payable by Ionis. Ionis expects to use approximately $420.4 million of the net proceeds from the offering to repurchase $434.1 million in aggregate principal amount of its 0.125% Convertible Senior Notes due 2024 (the "2024 notes") in privately negotiated transactions. Ionis expects to use the remaining net proceeds from the offering for additional repurchases of the 2024 notes from time to time following the offering, including the repayment of any remaining 2024 notes at maturity, and for general corporate purposes.

Before March 15, 2028, holders will have the right to convert their notes only upon the satisfaction of specified conditions and during certain periods. On or after March 15, 2028 until the close of business on the second scheduled trading day immediately preceding the maturity date, holders may convert all or any portion of their notes at any time. Upon conversion, Ionis will pay or deliver, as the case may be, cash, shares of its common stock or a combination of cash and shares of its common stock, at its election. The conversion rate for the notes will initially be 18.6120 shares of Ionis’ common stock per $1,000 principal amount of notes (equivalent to an initial conversion price of approximately $53.73 per share of Ionis’ common stock). The initial conversion price represents a premium of approximately 32.5% over the last reported sale price of $40.55 per share of Ionis’ common stock on June 7, 2023. The conversion rate will be subject to adjustment in some events but will not be adjusted for any accrued or unpaid interest.

Ionis may not redeem the notes prior to June 20, 2026. Ionis may redeem for cash all or any portion of the notes (subject to certain limitations), at its option, on or after June 20, 2026 if the last reported sale price of Ionis’ common stock has been at least 130% of the conversion price for the notes then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which Ionis provides notice of redemption at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date. However, Ionis may not redeem less than all of the outstanding notes unless at least $100.0 million aggregate principal amount of notes are outstanding and not called for redemption as of the time Ionis sends the related notice of redemption. No sinking fund is provided for the notes.

If Ionis undergoes a "fundamental change" (as defined in the indenture that will govern the notes), then, subject to certain conditions and limited exceptions, holders may require Ionis to repurchase for cash all or any portion of their notes at a fundamental change repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date or if Ionis delivers a notice of redemption, Ionis will, in certain circumstances, increase the conversion rate for a holder who elects to convert its notes in connection with such a corporate event or convert its notes called (or deemed called) for redemption in connection with such notice of redemption, as the case may be.

In connection with any repurchase of the 2024 notes, Ionis expects that holders of the 2024 notes who agree to have their 2024 notes repurchased and who have hedged their equity price risk with respect to such notes (the "hedged holders") will unwind all or part of their hedge positions by buying Ionis’ common stock and/or entering into or unwinding various derivative transactions with respect to Ionis’ common stock. The amount of Ionis’ common stock to be purchased by the hedged holders or in connection with such derivative transactions may be substantial in relation to the historic average daily trading volume of Ionis’ common stock. This activity by the hedged holders may result in an increase in the effective conversion price of the notes.

The notes and any shares of Ionis’ common stock issuable upon conversion of the notes have not been and will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities 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 the registration or qualification thereof under the securities laws of any such state or jurisdiction.

On June 8, 2023 Aviko Radiopharmaceuticals, a Deerfield Management-founded biotechnology company developing medicines to unlock the potential of boron neutron capture therapy (BNCT), and Neutron Therapeutics, the leading provider of accelerator-based neutron systems for targeted radiation therapy of solid tumors, reported the formation of a strategic partnership to advance BNCT to treat cancer (Press release, Aviko Radiopharmaceuticals, JUN 8, 2023, View Source [SID1234632629]). The partnership aligns the companies’ efforts to build the first BNCT treatment center in the United States and to establish additional BNCT facilities through collaborations with premier academic medical centers.

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"To bring BNCT to patients in need, it’s critical to foster collaboration among key stakeholders who are working to advance this precision medicine modality," said Dave Greenwald, Ph.D., chief executive officer of Aviko and vice president of business development at Deerfield. "This strategic partnership brings together Aviko’s expertise in drug development and Neutron’s industry-leading neutron delivery technology with the goal of improving outcomes for patients with a variety of cancers."

BNCT involves a non-toxic boron medicine that is designed to accumulate in cancer cells. The boron medicine remains inert until it is irradiated by safe, low-energy neutrons at the site of the tumor, releasing alpha particles that destroy cancerous cells. Aviko has developed a pipeline of boron medicines that exhibit properties to enable effective BNCT, including high tumor selectivity. Neutron’s nuBeam system is a comprehensive BNCT treatment suite with an accelerator that produces the highest neutron flux available in the clinical setting, leading to potentially shorter treatment times and improved patient experience.

"BNCT has demonstrated the ability to eradicate tumors in as few as one or two treatments, while minimizing damage to healthy tissue," said Elizabeth Reczek, Ph.D., chief executive officer of Neutron Therapeutics. "We’re thrilled to partner with Aviko in our efforts to expand BNCT as a treatment modality in the U.S. and globally."

Neutron has installed its nuBeam system at Helsinki University Hospital in Helsinki, Finland, and at Shonan Kamakura General Hospital in Kamakura City, Kanagawa prefecture, Japan.

"Recent innovations related to neutron acceleration have expanded the opportunities for BNCT to be used in a wide range of medical centers," said Bill Buckley, co-founder of Neutron Therapeutics and founder of New Zealand-based Buckley Systems. "This partnership is an example of how two companies can collaborate to advance a promising therapy to help patients who are in need of more effective treatment options."

Ted Smick, chief technology officer and co-founder of Neutron Therapeutics, added: "Together, Aviko and Neutron Therapeutics offer a complete solution for BNCT, enabling more medical centers to provide this powerful new treatment to patients."

On June 8, 2023 Perspective Therapeutics, Inc. ("Perspective" or "the Company") (NYSE AMERICAN: CATX), a precision oncology company developing alpha-particle therapies and complementary diagnostic imaging agents and an innovator in seed brachytherapy treatment options for multiple cancers, reported it will have four presentations at the 2023 Annual Society for Nuclear Medicine and Molecular Imaging (SNMMI) Conference being held in Chicago from June 24-27, 2023 (Press release, Perspective Therapeutics, JUN 8, 2023, View Source [SID1234632616]).

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"Our team at Perspective Therapeutics continues to make progress across all aspects of development, including the generation of promising clinical data. We are delighted to present the latest research on our products at the SNMMI annual conference. Targeted alpha therapies are emerging as a class of drugs with significant potential to revolutionize cancer treatment, and our team and collaborators keep building on the increasingly strong foundation of solid scientific data coming from our platform," said Thijs Spoor, Perspective’s Chief Executive Officer.

Michael Schultz, Chief Science Officer of Perspective Therapeutics, stated, "I would like to thank our excellent team of scientists and our collaborators for the work they continue to do across the spectrum of drug development. The data to be presented at this conference reflects the breadth of our expertise, from target discovery to isotope generation, finished product manufacture, preclinical experiments in cancers with high unmet need, and finally translation of these products into patient care. We believe that our work has the potential to make a real difference in the lives of cancer patients and we have a world class team driving us forward."

Presentation Summaries

Presentation #1: "Targeted imaging of melanoma for alpha-particle radiotherapy (TIMAR) trial"

This will be a presentation of the initial First-in-Human data from Perspective’s MC1R-targeted VMT01/02 imaging study conducted at the Mayo Clinic, Rochester. The presented results will discuss the safety and suitability of [203Pb]VMT01 or [68Ga]VMT02 for selection of patients and organ and tumor dosimetry calculations for the therapeutic alpha emitter [212Pb]VMT01.

The presentation will be during the Scientific Session 25 (Head/Neck and Melanoma) on Monday, June 26, 2023, 10:15 AM – 10:25 AM, by Geoffrey B. Johnson MD PhD, Head of Nuclear Medicine, Mayo Clinic (Rochester, MN USA).

Presentation #2: "Targeted alpha therapy of [212Pb] VMT-α-NET in a metastatic neuroblastoma model"

This presentation will discuss the Company’s continued work to expand the use of its clinical stage [212Pb]VMT-α-NET product into additional oncology indications with high unmet need, such as pediatric neuroblastoma. Preclinical model development and the results of therapy with Perspective’s product will be presented.

The presentation will occur during the Scientific Session 36 New Directions in Oncology – Preclinical and Translational 2 on Tuesday, June 27, 2023, 10:05 AM – 10:15 AM by Dijie Liu PhD DVM, Principal Research Scientist, Perspective Therapeutics.

Presentation #3: "Radiosynthesis of 212Pb labelled VMT-α-NET for clinical use"

Targeted alpha-particle radiotherapies (TATs) have been evolving as promising treatments in management of cancers. 212Pb represents an isotope with decay properties and half life that are well-suited for peptide based radiopharmaceutical therapies. Investigators from Fortis Hospital have reported responses to treatment with [212Pb]VMT-a-NET. Here, the radiopharmaceutical production and quality control of [212Pb]VMT-a-NET is presented for clinical use.

The Presentation will occur during the Integrated Session 11 Novel Radiometals on Tuesday, June 27, 2023, 2:00 PM – 3:15 PM by A by Parul Thakral, PhD, Clinical Research Officer at Fortis Memorial Research Institute, Gurgaon – India (Co-author Michael K Schultz PhD, CSO Perspective Therapeutics).

Presentation 4: "Production and purification of high specific activity lead-203 (203Pb) for preclinical applications"

Lead-203 (203Pb) and Lead-212 (212Pb) have emerged as a matched pair for the development of elementally matched theranostic radiopharmaceuticals. 203Pb decays to 203Tl by electron capture (EC) and emits photons suitable for SPECT imaging (279 keV, 81%, t1/2 = 2.16 d) while 212Pb (t1/2 = 10.64 h) decays by emission of β– and α-particles suitable for targeted radiotherapy. Here, the investigators aimed to develop robust methods for production and separation of 203Pb from enriched Tl (205Tl) target material suitable for radiochemistry and preclinical studies.

The Presentation will occur during the Integrated Session 11 Novel Radiometals on Tuesday, June 27, 2023, 2:00 PM – 3:15 PM by A. Shefali Saini, PhD Candidate, University of Alabama, Birmingham (Mentor Professor Suzanne Lapi PhD) (Co-author Michael K Schultz PhD, CSO Perspective Therapeutics).

On June 9, 2023 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported updated clinical and translational data on its clinical trial BALLI-01 (evaluating UCART22) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 (Press release, Cellectis, JUN 8, 2023, View Source [SID1234632606]). The data presented support the preliminary safety and efficacy of UCART22 in a heavily pretreated relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) population.

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"These clinical data are very positive for patients with r/r B-ALL who have failed multiple lines of treatment options including chemotherapy, CD19 directed CAR T-cell therapy and allogeneic stem cell transplant and encourage further enrollment into the BALLI-01 clinical study" said Nicolas Boissel, M.D., Ph.D., Head of Hematology Adolescent and Young Adult Unit at Hôpital Saint-Louis, Paris, France.

The poster presentation at EHA (Free EHA Whitepaper) highlights the following data:

BALLI-01 is a Phase 1/2a open-label study, evaluating the safety and clinical activity of UCART22 in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

The poster presentation reviewed clinical and translational data from patients who received UCART22 after lymphodepletion (LD) with fludarabine and cyclophosphamide (FC) (F : 30 mg/m2 × 3d, C : 1.0 g/m2 × 3d) or fludarabine, cyclophosphamide and alemtuzumab (FCA) (F: 30 mg/m2 × 3d, C : 0.5g/m2 × 3d, A : 20 mg/d × 3d) in patients with r/r B-ALL.

Compared to the clinical update on BALLI-01 at ASH (Free ASH Whitepaper) 2021, the poster presents data from six additional patients who received UCART22 at dose level 3 (DL3), 5 x 106 cells/kg, as of the December 31, 2022 data cutoff.

Preliminary safety data

UCART22 administered after FC or FCA LD regimen was well tolerated. No dose limiting toxicities (DLTs) nor immune effector cell-associated neurotoxicity syndrome (ICANS) were observed; 61% of patients reported cytokine release syndrome (CRS) (Grade 1 [N=9] or Grade 2 [N=2]). One serious adverse event of special interest (AESI) of Grade 2 graft-versus-host disease (GvHD) (skin) was reported in the setting of reactivation of prior allogeneic hematopoietic stem cell transplantation (HSCT) donor stem cells. Serious adverse events (SAEs) (G≥3) reported in 72% of patients included infections (39%) and febrile neutropenia (28%), and all were not related to UCART22.

Preliminary efficacy data

Responses were assessed beginning on Day 28.

Up to FC/FCA-Intermediate Dose Level 2 (DL2i): 3 complete remissions with incomplete count recovery (CRi) and 1 morphologic leukemia-free state (MLFS) were observed and previously reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 conference.

For FCA-Dose Level 3 (DL3), 50% of the six patients responded:

– 1 patient who failed 4 prior lines, including multiagent chemotherapy, blinatumomab, inotuzumab, autologous CAR19, and allogeneic HSCT, achieved a minimal residual disease (MRD) negative complete response (CR) lasting over 90 days after UCART22 infusion as of the December 31, 2022 data cutoff.

– 1 patient who failed 4 prior lines, including multiagent chemotherapy, venetoclax, autologous CAR19, and allogeneic HSCT, achieved an MRD negative complete response with incomplete count recovery (CRi) consolidated with donor lymphocyte infusion (DLI) after Day 90 and remains in an MRD negative CRi past 7 months as of the December 31, 2022 data cutoff.

– 1 patient who failed 3 prior lines, including multiagent chemotherapy, venetoclax, autologous CAR19, and allogeneic HSCT, achieved an MRD negative MLFS up to Day 114.

Host lymphocytes remained suppressed (mean ALC <0.1 x103 cells/mL) through Day 28 for all patients who received FCA LD. Peak ferritin levels correlated with UCART22 cell expansion and cytokine release syndrome (CRS). UCART22 continues to be safe and tolerable, with no treatment emergent serious adverse events (TEAEs) or DLTs reported. UCART22 cell expansion was detected in 9 of 13 patients in the FCA LD arm and associated with clinical activity.

Overall, these data support the preliminary safety and efficacy of UCART22 in this heavily pretreated r/r B-ALL population.

The BALLI-01 study is currently enrolling patients after FCA lymphodepletion. UCART22 is currently the most advanced allogeneic CAR T-cell product in development for r/r B-ALL. The next data set is expected to be released later this year.

On June 8, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported Sanofi’s news that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for SAR’579 / IPH6101 for the treatment of hematological malignancies (Press release, Innate Pharma, JUN 8, 2023, View Source [SID1234632601]).

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Fast Track Designation is an FDA process designed to facilitate the development, and expedite the review of, medicines to treat serious conditions and fill unmet medical need. The FDA created this process to help deliver important new drugs to patients earlier, and it covers a broad range of serious illnesses.

SAR’579, ANKET platform lead asset, is a trifunctional anti-CD123 NKp46×CD16 NK cell engager from a joint research collaboration between Innate Pharma and Sanofi, now under development by partner Sanofi.

"It is promising to see SAR’579 / IPH6101 was granted Fast Track Designation in the US for the treatment of hematological malignancies, and congratulate our partner Sanofi on this milestone," said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "In addition to the encouraging clinical data recently presented at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting, this FDA Fast Track Designation further validates the potential of the ANKET platform to treat cancer patients with NK Cell Engagers."

About ANKET

ANKET (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer.

This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.