PacBio Announces a Private Convertible Exchange Transaction of $441 Million Principal Amount of 1.375% Convertible Senior Notes due 2030

On June 26, 2023 Pacific Biosciences of California, Inc. ("PacBio") (NASDAQ: PACB) reported that it has entered into a privately negotiated exchange agreement with a holder of PacBio’s outstanding 1.50% Convertible Senior Notes due 2028 (the "2028 Notes"), pursuant to which PacBio will issue $441 million principal amount of its 1.375% Convertible Senior Notes due 2030 (the "New Notes") in exchange for $441 million principal amount of the 2028 Notes (the "Exchange Transaction"), in a transaction exempt from registration under the Securities Act of 1933, as amended, and the rules and regulations thereunder (Press release, Pacific Biotech, JUN 26, 2023, View Source;301861431.html [SID1234632914]). The Exchange Transaction is expected to close on or about June 30, 2023, subject to customary closing conditions.

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"In 2021, we issued $900 million in convertible notes due in 2028, enabling us to scale the company for growth. By exchanging a portion of these notes, we have extended the duration of our debt, and with our plans to achieve positive cash flows during 2026, this further strengthens our financial position and gives us greater flexibility," said Christian Henry, President and Chief Executive Officer of PacBio. "This exchange agreement comes at an opportune time as we bring some of the most innovative sequencing solutions to the market."

The New Notes will have an initial conversion rate of 46.5116 shares of PacBio’s common stock ("common stock") per $1,000 principal amount of the New Notes (which is equal to an initial conversion price of approximately $21.50 per share of common stock), subject to customary anti-dilution and other adjustments. The Notes will mature on December 15, 2030, unless earlier repurchased, redeemed or converted. The Notes will pay interest semi-annually on each June 15 and December 15, commencing on December 15, 2023, at a rate of 1.375% per annum. Upon conversion, the Company will have the right to elect settlement in cash, shares of common stock or any combination thereof in its sole discretion.

In exchange for issuing the New Notes pursuant to the Exchange Transaction, PacBio will receive and cancel the exchanged 2028 Notes. Following the closing of the Exchange Transaction, $459 million in aggregate principal amount of 2028 Notes will remain outstanding with terms unchanged.

Additional information regarding this announcement may be found in a Current Report on Form 8-K that the Company intends to file today with the U.S. Securities and Exchange Commission.

Goldman Sachs & Co. LLC acted as exclusive financial advisor to PacBio in connection with the Exchange Transaction.

Fusion Pharmaceuticals to Present Interim Data from Phase 1 Trial of FPI-1434 in Patients with Solid Tumors Expressing IGF-1R

On June 26, 2023 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported the presentation of interim data from the dose escalation portion of the Phase 1 trial of [225Ac]-FPI-1434 (FPI-1434) in patients with solid tumors expressing IGF-1R (Press release, , JUN 26, 2023, View Source [SID1234632913]). The data will be presented by Neeta Pandit-Taskar, M.D., of Memorial Sloan Kettering Cancer Center, tomorrow at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting and will include molecular imaging, safety and pharmacokinetics (PK) from two dosing regimens: one with FPI-1434 alone ("hot only"), and another in which a small dose of cold antibody (naked IGF-1R antibody without the isotope) is administered prior to each dose of FPI-1434 ("cold/hot"). The poster presentation is available via the SNMMI Annual Meeting mobile application.

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"Antibody drug conjugates (ADCs) have shown tremendous success recently, driven in part by the benefits of using more potent payloads. We believe that the high potency of alpha emitters in place of conventional chemical toxins represents the evolution of the ADC field and is a significant and underexploited opportunity. While much is known about optimal dosing levels and paradigms for small molecule radiopharmaceuticals against well-known targets like PSMA, there is comparatively less experience for antibody-based alpha therapies in solid tumors. Consequently, in the Phase 1 study of FPI-1434, we undertook a stepwise dose exploration, in patients with various cancer types expressing IGF-1R, that included three stages: (i) hot only regimen in a single ascending dose escalation; (ii) hot only regimen in a multiple ascending dose escalation; and (iii) cold/hot regimen in a multiple ascending dose escalation. Learnings from this multi-part study have taken us a step further towards unlocking the potential of antibody-based TATs as next-generation ADCs," said Chief Executive Officer John Valliant, Ph.D.

Dr. Valliant continued, "We are pleased to report data and key learnings from our first antibody targeted alpha therapy (TAT) program which showed pre-administration of cold antibody prior to administering radiolabeled FPI-1434 has the potential to significantly enhance the therapeutic index by driving more active drug to tumor sites with an improved safety profile compared to hot-only dosing. In addition, with pre-administration of cold antibody, only a fraction of the injected amount of radiation is needed to achieve comparable exposures to hot-only cohorts. Results show the pharmacokinetic profile of 15 kBq/kg in the cold/hot regimen is comparable to 40 kBq/kg hot only, with a safety profile that made it possible to deliver up to five cycles thus far. With encouraging safety, dosimetry, and PK results, as well as stable disease observed in two heavily pretreated patients despite a low dose, we are continuing evaluation of the cold/hot regimen at a higher dose level in Cohort 2. We expect to share those results around the end of 2023."

The Phase 1, multi-center, open-label clinical trial is designed to investigate the safety, tolerability and pharmacokinetics of FPI-1434 in patients with solid tumors expressing IGF-1R. The trial is also designed to establish the maximum tolerated dose for FPI-1434 and the recommended Phase 2 dose. As part of the precision medicine approach, prior to receiving the therapeutic injection of FPI-1434, patients are administered an indium-111 imaging analogue, [111In]-FPI-1547 (FPI-1547). The images collected are used to confirm the presence of tumor uptake and ensure that estimated radiation doses to organs and tissues are below protocol-specified safety limits.

Based on results from an imaging sub-study evaluating pre-administration of cold antibody prior to each dose of FPI-1547 that demonstrated a favorable gain in tumor lesion uptake versus normal tissue, the Company amended the Phase 1 trial protocol to evaluate both the hot only and cold/hot dosing regimens.

Cold/Hot Dosing Regimen
In the cold/hot arm, three patients were dosed in Cohort 1 at a dose of 15 kBq/kg following pre-administration of cold antibody. In Cohort 1, cold/hot dosing was observed to be safe with no treatment-related serious adverse events (SAEs) or dose limiting toxicities (DLTs). Absorbed dose to critical organs (kidney, liver and lungs) in this dosing regimen were less than 7% of defined limits, supporting continued dose escalation.

Pre-administration of cold antibody demonstrated improved tumor uptake while also reducing hematological toxicity observed in the hot only dosing arm. When normalized to 15 kBq/kg, the average lesion absorbed dose and dose/volume in the cold/hot arm were nearly double the level compared to hot only. Further, 15 kBq/kg in the cold/hot dosing arm shows comparable systemic exposure to approximately 40 kBq/kg of a hot only dose, but shows an improved hematological safety profile as measured by changes in platelet count.

Two heavily pre-treated patients from the cold/hot dosing arm received three and five cycles of treatment, with both achieving durable stable disease as their best response. The dose level from Cohort 1, while sufficient to demonstrate marked differences in tumor uptake and achieve stable disease, was expected to be sub-optimal with respect to efficacy.

Fusion is currently enrolling Cohort 2 in the cold/hot dosing regimen at 25 kBq/kg and expects to report data from this cohort around year-end 2023.

Hot Only Dosing Regimen
In the hot only multiple ascending arm, six patients were dosed across two cohorts. Dose-dependent decrease in blood counts, particularly thrombocytopenia, was identified as the most common type of adverse event related to FPI-1434, with Grade 4 thrombocytopenia observed at 75 kBq/kg and 55 kBq/kg. The Company has discontinued dosing in the hot only dosing arm and no longer plans to use this method of FPI-1434 administration.

"Given the known expression of IGF-1R on multiple cancers, Fusion believes in the opportunity for FPI-1434 to treat a broad array of cancer types," said Chief Medical Officer Dmitri Bobilev, M.D. "We believe that thrombocytopenia observed at higher dose levels in the hot only part of the trial, may result at least in part from direct effect of FPI-1434 on IGF-1R-expressing megakaryocytes and from Fc-mediated binding in normal tissues. The ability to use pre-administration of cold antibody to block the IGF-1R receptors on normal cells and non-target specific binding and deliver higher doses of radioactivity to tumor cells is highly encouraging. We look forward to sharing results from the second cohort."

Following the conclusion of the SNMMI Annual Meeting, the presentation can be found at View Source

Fusion Conference Call Information
Fusion will host a live conference call and webcast tomorrow beginning at 4:00 p.m. ET/3:00 p.m. CT to discuss the data presentation. To access the live call, please dial 1-877-870-4263 (U.S.), 1-855-669-9657 (Canada) or 1-412-317-0790 (international) and reference Fusion Pharmaceuticals. A webcast of the conference call will be available under "Events and Presentations" in the Investors & Media section of Fusion’s website at View Source The archived webcast will be available on Fusion’s website shortly after the conclusion of the call and will be available for 90 days following the event.

About FPI-1434
FPI-1434 is a radioimmunoconjugate designed to target and deliver alpha emitting medical isotopes to cancer cells expressing IGF-1R, a receptor that is overexpressed on many tumor types. FPI-1434 utilizes Fusion’s Fast-Clear linker to connect a human monoclonal antibody that targets IGF-1R with actinium-225, a powerful alpha-emitting isotope with desirable half-life and decay chain properties.

New ZIRCON Phase III Data Presented at SNMMI: Potential Utility of TLX250-CDx in Staging and Monitoring ccRCC

On June 26, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported further details of the positive results from its completed pivotal Phase III ZIRCON study of TLX250-CDx (89Zr-DFO-girentuximab) in clear cell renal cell carcinoma (ccRCC) (ClinicalTrials.gov Identifier: NCT03849118) (Press release, Telix Pharmaceuticals, JUN 26, 2023, View Source [SID1234632912]).

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New data demonstrates the ability of TLX250-CDx to detect extrarenal lesions, supporting potential clinical utility in the metastatic or recurrent setting, and for staging and informing treatment decisions.

TLX250-CDx PET/CT detected more lesions in liver and bone than diagnostic CT imaging alone. This reinforces the performance of this investigational diagnostic imaging agent across all analyses, with previously presented data showing an excellent overall sensitivity and specificity of 86% and 87%, respectively, together with high intra-reader agreement.[1], [2]

The results were featured in an oral presentation delivered on Monday, 26 June 2023 (CDT) by Jeremie Calais, MD, Director of the Clinical Research Program of the Ahmanson Translational Theranostics Division of the Department of Molecular and Medical Pharmacology at University of California, Los Angeles (UCLA), and a principal investigator in the Phase III ZIRCON study, at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2023 Annual Meeting in Chicago.

New data presented:

25 patients had ≥1 extrarenal lesions detected by whole body PET/CT (n=10), abdominal PET/CT (n=17), or both modalities (n=2)
Extrarenal lesions were mostly localised in bone, liver, lung, adrenal glands and lymph nodes
Jeremie Calais, MD commented, "It is a pleasure to be showcasing further results from Telix’s highly successful Phase III ZIRCON study at SNMMI, the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging worldwide. Data presented here in Chicago on extrarenal lesions demonstrates potential utility of TLX250-CDx for staging and monitoring high risk patients where there is a great deal of interest from the clinician community."

Telix is in the process of implementing an expanded access program in the United States and establishing named patient programs for TLX250-CDx in Europe.

Oncotarget Publishes New Data by Lantern Pharma, an AI Company Developing Cancer Therapies, Further Supporting Clinical Advancement of LP-284, a Novel Synthetically Lethal Drug Candidate for Non-Hodgkin’s Lymphomas

On June 26, 2023 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence ("AI") company developing targeted and transformative cancer therapies using its proprietary RADR AI and machine learning ("ML") platform with multiple clinical stage drug programs, reported that the company has published new findings in Oncotarget demonstrating drug candidate LP-284’s in vitro and in vivo antitumor potency for multiple non-Hodgkin’s lymphomas (NHL), including mantle cell lymphoma (MCL) and double-hit lymphoma (DHL) (Press release, Lantern Pharma, JUN 26, 2023, View Source [SID1234632908]). The journal article titled "LP-284 Targets Non-Hodgkin’s Lymphoma and DNA Damage Repair Deficiency" further supports LP-284’s development for NHL and advancement towards a first-in-human Phase 1 trial, which is anticipated for the second half of 2023.

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Non-Hodgkin’s lymphomas (NHL) remain one of the leading causes of cancer deaths globally and have an estimated 500,000 new cases globally, with NHL being the leading hematological malignancy in the US. Despite advances for NHL using combination and targeted therapies, nearly 20% to 40% of patients with certain subtypes still relapse after treatment. In aggressive subtypes of NHL, like MCL, nearly all patients relapse from standard-of-care (SOC) therapies.

"Given the efficacy of drug candidate LP-284 in preclinical studies and the mechanism of synthetic lethality where LP-284 seems to prefer blood cancers with deficiencies in the DNA repair pathways, we believe this drug candidate can be a powerful therapeutic option for a wide range of blood cancers with potential both as monotherapy in later stages of treatments and in earlier lines in combination with other agents," stated Panna Sharma, Lantern’s CEO and President. "We have developed this molecule from initial ideas to first-in-human clinical testing in a highly efficient and rapid manner by leveraging our AI platform, RADR. This is unheard of progress in oncology drug development and was achieved in less than 2.5 years and under $2 million USD, and we can readily scale the manufacturing of this molecule to meet global needs for NHL patients," continued Sharma.

"Our new findings in Oncotarget reveal that LP-284’s synthetically lethal mechanism of action is driven by the creation of double-strand DNA breaks and can be leveraged for multiple non-Hodgkin’s lymphomas that are DNA damage repair deficient," stated Kishor Bhatia, Ph.D., Lantern’s Chief Scientific Officer. "We have also demonstrated a critical preclinical finding that LP-284 has potent antitumor activity in MCL tumors that have grown resistant to standard-of-care agents. As nearly all patients with MCL relapse from standard-of-care treatment, they have an urgent and unmet need for potential new drug candidates, such as LP-284," continued Dr. Bhatia.

Key Publication Highlights:

LP-284’s mechanism of action, synthetic lethality, was demonstrated to be caused by LP-284’s induction of DNA double-strand breaks. Cells treated with LP-284 had significantly increased double-strand DNA breaks when compared to control-treated cells.
Nanomolar potency was demonstrated for LP-284 in 15 NHL cell lines, with the lowest IC-50s observed for the 6 MCL and 7 DHL/Triple Hit Lymphoma cell lines, which had average IC-50s of 342 nM and 613 nM respectively.
LP-284 treatment of 2 mg/kg and 4 mg/kg inhibited tumor growth of mice implanted with MCL xenografts by 63% and 113% respectively. LP-284’s tumor growth inhibition was greater than 2X that of the MCL SOC agents bortezomib or ibrutinib.
In mouse MCL xenograft tumors that had grown resistant to either bortezomib or ibrutinib, subsequent LP-284 treatment at 4 mg/kg led to near-complete tumor regression, whereas control-treated tumors continued to grow uncontrollably.
LP-284’s antitumor potency can be enhanced when combined with the FDA-approved agent spironolactone. Treatment of multiple myeloma cells with LP-284 + spironolactone led to a 2.4 fold decrease in IC-50 when compared to LP-284 treatment alone.
Combined, these new in vitro and in vivo results for LP-284 strongly support its anti-tumor activity for NHLs, including advanced MCL tumors that have grown resistant to SOC agents. Based on the potential of LP-284 for MCL, Lantern was granted an FDA Orphan Drug Designation for LP-284 in MCL.

The full journal article can be found on Lantern’s website or at the Oncotarget website. Oncotarget is primarily an oncology-focused, peer-reviewed, open-access journal which aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

POINT Biopharma Expands Its Research with Next-Generation Isotopes, Publishing New Preclinical Data at SNMMI’s Annual Congress

On June 26, 2023 POINT Biopharma Global Inc. (NASDAQ: PNT) (the "Company" or "POINT"), a company accelerating the discovery, development, and global access to life-changing radiopharmaceuticals, reported the publication of preclinical data from their pan-cancer, fibroblast activation protein-α (FAP)-targeted program, PNT2004, at the 2023 Annual Meeting of the Society of Nuclear Medicine & Molecular Imaging (SNMMI), taking place June 24-27, 2023, in Chicago, IL (Press release, Point Biopharma, JUN 26, 2023, View Source [SID1234632907]).

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PNT6555, the lead candidate in the PNT2004 program, led to complete and durable tumor regression and improved survival in HEK-mFAP tumor-bearing mice when chelated to any one of the three radioisotopes studied: lutetium-177 (177Lu), actinium-225 (225Ac), and terbium-161 (161Tb). Additionally, 177Lu-PNT6555 in combination with anti-PD-1 checkpoint blockade was assessed in the aggressive, immunocompetent CT26-mFAP mouse model and demonstrated a significant survival benefit compared to either treatment alone.

"By continuing to develop expertise in more isotopes, POINT is better positioned to create optimized next-generation radioligands, which match a ligand’s properties with the most appropriate isotope," said Joe McCann, Ph.D., Chief Executive Officer of POINT Biopharma. "The expertise to discover and develop new radioligands and advance them into clinical trials has been built into POINT. We look to fill our toolbox of isotopes as full as we can, evaluate them in discovery and development, and aim to bring forward candidates we believe could generate compelling patient benefit."

Presentation details are as follows:

Title: Preclinical application of novel isotopes and combination therapy with the FAP-targeted ligand PNT6555

Abstract ID: 180

Session Name: Imaging and Therapy in Preclinical Oncology Models – Session 2

Session Date: Monday, June 26th

Session Time: 10:00 AM – 11:15 AM CT

Presentation Time: 10:45 AM – 10:55 AM CT

Following the presentation of these data the poster will be made available on POINT’s Investor Relations website, View Source