On October 31, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical-stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported validation for the European patent 2019213664 titled "METHODS FOR PRODUCING (6S,15S)-3,8,13,18-TETRAAZAICOSANE-6,15-DIOL" in the United Kingdom, Italy, Germany, France, and Spain (Press release, Panbela Therapeutics, OCT 31, 2023, View Source;utm_medium=rss&utm_campaign=panbela-announces-validation-of-european-patent-for-claims-of-a-novel-process-for-the-production-of-sbp-101 [SID1234636548]). This patent, developed in collaboration with Syngene International Ltd., an integrated research, development, and manufacturing services company, claims a novel process with a reduced number of synthetic steps from seventeen to six to produce SBP-101, a lead investigational product. The patent is valid until 2039.

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Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela Therapeutics, commented, "We’re excited to have this European patent now validated in individual countries." First issued in the United States in 2021 and now in several other territories, this patent covers a shorter synthesis of SBP-101, which provides many benefits including a scalable, efficient and cost-effective manufacturing process to enable future commercialization. Jonathan Hunt, Managing Director and Chief Executive Officer, Syngene International Ltd., said, "Our partnership with Panbela exemplifies Syngene’s commitment to fostering innovation and collaboration in the pharmaceutical industry. Reducing the manufacturing steps of SBP-101 from seventeen to just six not only accelerates the delivery of this promising drug to patients but also underscores Syngene’s dedication to improving efficiency. This patent validation in certain European countries is a testament to our combined expertise and commitment to improving patient outcomes.

We are proud to stand alongside Panbela as we continue to push the boundaries of pharmaceutical innovation." Dr. Simpson added, "We are pleased with the continued growth of our patent portfolio with the validation in several European countries. With a pharmaceutical starting material that is more widely available and a process that is effective and scalable, this ensures a stable drug supply for current clinical trials and future endeavors."

About our Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention, ovarian cancer and diabetes. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101 Ivospemin

Ivospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. For more information, please visit View Source

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X Eflornithine

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity.

On October 31, 2023 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported its financial results for the third quarter ended September 30, 2023, raised 2023 net sales guidance for INGREZZA, and announced an Analyst Day to be held in New York City on December 5th (Press release, Neurocrine Biosciences, OCT 31, 2023, View Source [SID1234636546]).

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"With INGREZZA sales continuing to grow, an expanded indication to treat chorea associated with Huntington’s disease, and positive Phase 3 results in congenital adrenal hyperplasia, Neurocrine remains well positioned to build a leading neuroscience-focused company," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "We look forward to sharing more insight into our R&D portfolio and strategy at our December Analyst Day."

Three Months Ended

September 30,

Nine Months Ended

September 30,

(unaudited, in millions, except per share data)

2023

2022

2023

2022

Revenues:

Net Product Sales

$ 491.8

$ 379.3

$ 1,353.4

$ 1,036.3

Collaboration Revenue

7.0

8.6

18.5

40.4

Total Revenues

$ 498.8

$ 387.9

$ 1,371.9

$ 1,076.7

GAAP Research and Development (R&D)

$ 142.2

$ 107.7

$ 427.5

$ 345.8

Non-GAAP R&D

$ 125.0

$ 92.8

$ 372.7

$ 302.2

GAAP Selling, General and Administrative (SG&A)

$ 204.2

$ 186.3

$ 668.7

$ 569.8

Non-GAAP SG&A

$ 169.7

$ 158.1

$ 563.4

$ 483.8

GAAP Net Income

$ 83.1

$ 68.5

$ 102.0

$ 65.5

GAAP Earnings Per Share – Diluted

$ 0.82

$ 0.69

$ 1.01

$ 0.67

Non-GAAP Net Income

$ 156.1

$ 106.7

$ 232.3

$ 218.5

Non-GAAP Earnings Per Share – Diluted

$ 1.54

$ 1.08

$ 2.31

$ 2.22

(unaudited, in millions)

September 30,

2023

December 31,

2022

Total Cash, Cash Equivalents and Marketable Securities

$ 1,549.8

$ 1,288.7

Third Quarter INGREZZA Net Product Sales Highlights:

INGREZZA third quarter 2023 net product sales were $486 million and grew 29% vs. the third quarter 2022 driven by prescription demand
Continued high level of new patient scripts generated in the third quarter of 2023
Third Quarter Financial Highlights:

Third quarter 2023 GAAP net income and earnings per share of $83 million and $0.82, respectively, compared with $69 million and $0.69, respectively, for third quarter 2022
Third quarter 2023 non-GAAP net income and earnings per share of $156 million and $1.54, respectively, compared with $107 million and $1.08, respectively, for third quarter 2022
Differences in third quarter 2023 GAAP and non-GAAP operating expenses compared with third quarter 2022 driven by:
Increased R&D expense in support of an expanded and advancing clinical portfolio including preclinical investments in VMAT2, crinecerfont, and our muscarinic compounds
Increased SG&A expense primarily due to ongoing commercial initiatives supporting INGREZZA growth including the expanded indication to treat chorea associated with Huntington’s disease
At September 30, 2023, the Company had cash, cash equivalents and marketable securities of approximately $1.5 billion
A reconciliation of GAAP to non-GAAP financial results can be found in Table 3 and Table 4 at the end of this earnings release.

Recent Events:

In August 2023, the FDA approved INGREZZA for the treatment of adults with chorea associated with Huntington’s disease.
In September 2023, the Company announced the FDA accepted its New Drug Application (NDA) for INGREZZA oral granules, a new sprinkle formulation of INGREZZA capsules for oral administration. The agency set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024.
In September 2023, the Company announced positive top-line data from the Phase 3 CAHtalyst clinical study of crinecerfont in adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). The study met its primary as well as important key secondary endpoints.
In October 2023, the Company announced positive top-line data from the Phase 3 CAHtalyst clinical study of crinecerfont in pediatrics with CAH due to 21-hydroxylase deficiency (21-OHD). The study met both its primary and key secondary endpoint.
Updated 2023 INGREZZA Sales Guidance and Operating Expense Guidance:

Range

(in millions)

Low

High

INGREZZA Net Product Sales 1

$ 1,820

$ 1,840

GAAP R&D Expense 2

$ 560

$ 570

Non-GAAP R&D Expense 3

$ 490

$ 500

GAAP and Non-GAAP IPR&D 4

$ 144

$ 144

GAAP SG&A Expense 5

$ 870

$ 890

Non-GAAP SG&A Expense 3

$ 740

$ 760

1. INGREZZA sales guidance for fiscal 2023 reflects expected sales of INGREZZA.

2. GAAP R&D guidance includes amounts for milestones that are probable of achievement or have been achieved.

3. Non-GAAP guidance adjusted primarily to exclude estimated non-cash stock-based compensation expense of $70 million in R&D and $125 million in SG&A.

4. IPR&D guidance reflects acquired in-process research and development once significant collaboration and licensing arrangements have been completed. IPR&D guidance includes $143.9 million associated with the new strategic collaboration with Voyager.

5. SG&A guidance range reflects increased spend following INGREZZA expanded indication to treat chorea associated with Huntington’s disease and positive Phase 3 results in CAH.

Conference Call and Webcast Today at 8:00 AM Eastern Time
Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-895-3361 (US) or 785-424-1062 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine Biosciences’ website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

On October 31, 2023 Myriad Genetics, Inc. (the "Company") reported to have entered into an amendment (the "Amendment") to (i) its original credit agreement (the "Original Credit Agreement") dated as of June 30, 2023, with the lenders from time to time party thereto, certain of the Company’s domestic subsidiaries party thereto (the "Guarantors"), and JP Morgan Chase Bank, N.A., as Administrative Agent (in such capacity, "Administrative Agent") and as Issuing Bank, consisting of a revolving credit facility in an initial maximum principal amount of $90,000,000, with an option to increase the maximum principal amount by up to $25,000,000 and (ii) its original pledge and security agreement (the "Original Security Agreement") dated as of June 30, 2023, with the other grantors party thereto and the Administrative Agent (Filing, 8-K, Myriad Genetics, OCT 31, 2023, View Source [SID1234636541]). Pursuant to the Amendment, the Company exercised the option to increase the maximum principal amount of the available revolving line of credit by $25,000,000, which was effectuated through a new commitment provided by a new lender, Goldman Sachs Bank USA.

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In addition, the Amendment amends the Original Credit Agreement and Original Security Agreement to, among other things, the following:

•allow for the assignment and terminations of certain lease agreements and the sale of certain personal property consisting of office furniture and equipment relating to such assignment;
•extend the time for compliance with certain post-closing obligations of the Original Credit Agreement; and
•revise the language of the Original Security Agreement to better reflect the Company’s existing cash management system.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the complete text of the Amendment, a copy of which is attached as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference in its entirety.

On October 31, 2023 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the company’s Phase 1 clinical trial of XMT-2056 (Press release, Mersana Therapeutics, OCT 31, 2023, View Source [SID1234636539]). XMT-2056 is a systemically administered Immunosynthen STING-agonist ADC that is designed to target a novel human epidermal growth factor receptor 2 (HER2) epitope and locally activate STING signaling in both tumor-resident immune cells and in tumor cells, providing the potential to treat patients with HER2-high or -low tumors as monotherapy and in combination with standard-of-care agents.

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"An in-depth analysis of cytokine, pharmacokinetic and other clinical data from patients enrolled in our Phase 1 trial indicated that XMT-2056 is a highly potent innate immune agonist," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "Based on these data and with patient safety at the forefront of our efforts, we have lowered the starting dose in our Phase 1 dose escalation design. We are pleased to have aligned with FDA on the path forward and are excited to have the opportunity to continue to investigate the potential of XMT-2056 and our Immunosynthen ADC platform in the clinic."

The multicenter Phase 1 open-label trial is investigating XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal and non-small-cell lung cancers. The dose escalation and dose expansion portions of the trial will evaluate and characterize the relationship of safety, tolerability and exposure of XMT-2056 and this candidate’s preliminary anti-tumor activity, as measured by overall response rate, duration of response and disease control rate.

The FDA has granted orphan drug designation to XMT-2056 for the treatment of gastric cancer. In August 2022, Mersana entered into a global collaboration providing GSK plc with an exclusive option to co-develop and commercialize XMT-2056. GSK has not exercised this option to date.

On October 31, 2023 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, reported new nonclinical data at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) on innovations designed to shorten tumor infiltrating lymphocyte (TIL) manufacturing, LYL119, its second generation ROR1-targeted CAR T cell product candidate, as well as data on new technologies and the design of its two clinical trials in progress (Press release, Lyell Immunopharma, OCT 31, 2023, View Source [SID1234636536]).

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"We remain confident that generating T cells with the ability to resist exhaustion and qualities of durable stemness will unlock the potential of effective cell therapy for solid tumors, and our SITC (Free SITC Whitepaper) presentations highlight the progress we are making across our robust pipeline of product candidates and platform technologies designed to achieve this," said Gary Lee, Ph.D., chief scientific officer at Lyell. "We also highlight new data on our Epi-R P2 manufacturing process, a manufacturing innovation designed to enable faster delivery of TIL product to patients without sacrificing the desired yield, stemness phenotype and retention of tumor reactive clones."

Details on the presentations are below.

New Nonclinical Data on LYL119, Innovation in Manufacturing and New Technologies

Four presentations highlight new nonclinical data from Lyell’s product pipeline and research programs, including:

Lyell’s novel Epi-R P2 manufacturing protocol to shorten delivery time of TIL product to patients
New nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell therapy
A new technology being advanced through a collaboration between Lyell and Outpace to enable tumor-restricted IL-12 activity to enhance solid tumor T cell therapies
Lyell’s rejuvenation technology which has shown the potential to "turn back" the epigenetic clock to generate more stem-like T cells with reduced epigenetic age and enhanced proliferation ability
A presentation titled "Epi-R P2 protocol produces a scalable polyclonal TIL product with a greater expansion success rate across hot and cold tumors in shorter culture time" highlights Lyell’s Epi-R P2 manufacturing protocol that shortens manufacturing time for TIL while maintaining the desired yield, stemness phenotype and retention of tumor reactive clones. Current TIL production time is approximately four to six weeks. Literature suggests that a shorter culture time is associated with improved cell quality, functionality and positive clinical outcomes in metastatic melanoma patients. Lyell’s Epi-R manufacturing protocols are designed to generate populations of TIL with stem-like properties to potentially improve antitumor activity. Epi-R P2 is an improved TIL manufacturing process that reduces the TIL culture duration to less than three weeks without impacting the quality of TIL.

Presentation details: Abstract # 379, Friday, Nov. 3, 12–1:30 p.m. and 5:10–6:40 p.m.
New nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell therapy, is highlighted in a presentation titled "Preclinical development of LYL119, a ROR1-targeted CAR T-cell product incorporating four novel T-cell reprogramming technologies to overcome barriers to effective cell therapy for solid tumors." LYL119 incorporates four of Lyell’s complementary, stackable T-cell reprogramming technologies to create potent ROR1-targeted CAR T cells with durable function. In this study, LYL119 demonstrated superior cytotoxicity and sustained cytokine production upon repeated antigen stimulation compared to various controls lacking one or more of the reprogramming technologies and showed robust in vivo antitumor efficacy in a mouse xenograft tumor model at very low cell doses.

Presentation details: Abstract #278, Saturday, Nov. 4, 2023, 11:55–1:25 p.m. and 7–8:30 p.m.
A presentation titled "Protein design and inducible expression allow context-dependent, localized IL-12 activity to enhance solid tumor T cell therapies" highlights an innovative tumor-restricted IL-12 (trIL-12) technology that delivers potent IL-12 stimulation at the tumor site while avoiding systemic exposure. IL-12 is an immune-stimulatory cytokine that can induce potent anti-tumor activity, but systemic delivery of IL-12 has been shown to cause severe toxicity in patients. trIL-12 was designed leveraging Outpace’s OutSmart technology to rapidly auto-inactivate IL-12 after inducible secretion from engineered T cells with the aim of achieving safe, local delivery of IL-12 activity. trIL-12 is being advanced under a collaboration between Lyell and Outpace with the goal of improving efficacy for T-cell therapies while maintaining a favorable safety profile.

Presentation details: Abstract #1047, Friday, Nov. 3, 12–1:30 p.m. and 5:10–6:40 p.m.
A presentation titled "Rejuvenation of tumor-infiltrating lymphocytes (TIL) through Partial Reprogramming" describes Lyell’s rejuvenation technology which has shown the potential to "turn back" the epigenetic clock to generate more stem-like T cells with reduced epigenetic age and enhanced proliferation ability. Previously published studies have demonstrated the decline in T-cell function as a person ages. These new nonclinical data show TIL rejuvenated with Lyell’s technology retain a broad TCR repertoire and demonstrate improved T-cell function and antitumor properties.

Presentation details: Abstract #393, Friday, Nov. 3, 2023, 12–1:30 p.m. and 5:10–6:40 p.m.
Clinical Trials in Progress

Two additional presentations highlight the design of Lyell’s two ongoing Phase 1 clinical trials in progress.

A presentation titled "Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell therapy enhanced with genetic and epigenetic reprogramming, in advanced triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC)" describes the design of this dose-escalation, dose-expansion Phase 1 trial in patients with ROR1-positive relapsed refractory TNBC and NSCLC.

Presentation details: Abstract #754, Saturday, Nov. 4, 2023, 11:55–1:25 p.m. and 7–8:30 p.m.
A presentation titled "Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte (TIL) therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors" describes the design of this dose-escalation, dose-expansion Phase 1 trial in advanced solid tumors, including advanced melanoma, NSCLC and colorectal cancer

Presentation details: Abstract #747, Friday, Nov. 3, 2023, 12–1:30 p.m. and 5:10–6:40 p.m.