On December 15, 2022 Partner Therapeutics, Inc. (PTx) reported publication of a single institution retrospective cohort review of 15 patients with pediatric malignancies and invasive fungal diseases that were refractory to antifungal therapy and treated adjunctively with Leukine (sargramostim; yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) (Press release, Partner Therapeutics, DEC 15, 2022, View Source [SID1234625334]). Additionally, the publication included a systematic review of 50 published reports of rhu GM-CSF use for invasive fungal disease. Open Forum Infectious Diseases published the manuscript entitled "Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases." Leukine is not approved to treat invasive fungal disease.

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The authors conclude: "Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory [invasive fungal diseases] IFDs." The overall response rate for sargramostim use in the retrospective cohort was 92%. 80% of patients were refractory to antifungal therapy prior to sargramostim use. The infections were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Scedosporium sp), as well as the mucormycosis-causing pathogens Rhizopus sp., Lichtheimia sp.

Endogenous GM-CSF functions as a hematopoietic growth factor while also regulating the broader immune system via activation of macrophages, monocytes, and neutrophils.2 GM-CSF enhances macrophage activities such as pathogen killing and clearance as well as neutrophil fungicidal activity.3 Based on the mechanism of endogenous GM-CSF, clinicians have utilized Leukine adjunctively in treating infections, as summarized in the publication.1

The research was led by Thomas J. Walsh, MD, PhD (Hon), FIDSA, FAAM, FECMM, of the Transplantation-Oncology Infectious Disease Program at Weill Cornell Medicine and Center for Innovative Therapeutics and Diagnostics, and Tempe K. Chen, MD, of MemorialCare Miller Children’s & Women’s Hospital Long Beach and Division of Infectious Diseases at University of California Irvine School of Medicine. Dr. Walsh shared the significance of this work: "Building upon laboratory investigations of GM-CSF and pathogenic fungi that we have conducted; this paper is especially important as the translational evidence of sargramostim’s efficacy in managing invasive fungal disease in immunocompromised pediatric and adult patients. The paper imparts clinical significance to more recent preclinical data supporting the role of GM-CSF in mucosal host defenses and macrophage bioenergetics."

Bioenergetics refers to how cells transform energy. GM-CSF signaling regulates mitochondrial bioenergetics critical to macrophage function including energy utilization, cellular metabolism, and expression of mitochondrial proteins.

Dr. Mahmoud Ghannoum, Director of Integrated Microbiome Core and Center for Medical Mycology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, added: "A host directed therapy such as sargramostim (Rh GM-CSF) is a promising approach to treatment of intracellular pathogens, especially in the immune compromised patient. By attempting to restore the patient’s immune processes physicians may have a new tool to combat the development of antifungal resistance." This October, the World Health Organization (WHO) Antimicrobial Resistance Division issued a report to focus and drive policy interventions to strengthen the response to fungal infections with antifungal resistance. The pathogens were ranked into three priority groups: critical, high, and medium. All of the pathogens treated with Leukine in this review were due to pathogens classified as critical or high threats due to their distribution and antifungal resistance patterns.

PTx has a broad development program in place for Leukine including clinical investigations for the treatment of infectious diseases.

References

Chen TK, Batra JS, Michalik DE, et al. Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. Open Forum Infect Dis. 2022;9(11):ofac535. doi: 10.1093/ofid/ofac535
Metcalf D, Begley CG, Johnson GR, et al. Biologic properties in vitro of a recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1986;67(1):37-45. doi: 10.1182/blood.V67.1.37.37
Damiani G, McCormick TS, Leal LO, Ghannoum MA. Recombinant human granulocyte macrophage-colony stimulating factor expressed in yeast (sargramostim): A potential ally to combat serious infections. Clin Immunol. 2020;210:108292. doi:10.1016/j.clim.2019.108292
ABOUT LEUKINE

LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast.

LEUKINE is indicated:

To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).

For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients.

For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older.

For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.

For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.

To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).
Important Safety Information for Leukine (sargramostim)

Contraindications

Do not administer LEUKINE to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of LEUKINE.
Warnings and Precautions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If a serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy, and institute medical management. Discontinue LEUKINE permanently for patients with serious allergic reactions.

LEUKINE can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed.

LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.

Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after LEUKINE administration. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored.

Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.

If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half. Monitor complete blood counts (CBC) with differential twice per week.

Discontinue LEUKINE therapy if tumor progression, particularly in myeloid malignancies, is detected during LEUKINE treatment.

Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed.

Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants.
Drug Interactions

Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects.
Adverse Reactions

Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are:

In recipients of autologous bone marrow transplantation (BMT)–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
In recipients of allogeneic BMT–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
In patients with AML–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema

On December 15, 2022 Jacobio Pharma (1167. HK) reported that the Company’s in-house KRAS G12C inhibitor JAB-21822 was granted breakthrough therapy designations for the second line and above treatment of advanced or metastatic non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (Press release, Jacobio Pharmaceuticals, DEC 15, 2022, View Source [SID1234625333]). The designation was granted based on the solid clinical efficacy and safety data of JAB-21822. It will help expedite the program registration to health authority and accelerate its early access to the patients.

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The Phase II pivotal clinical trial of JAB-21822 was approved in China on September 5, 2022. The multi-center, single-arm, open-label study aims to evaluate the efficacy and safety of JAB-21822 as a single agent for the treatment of NSCLC patients with KRAS G12C mutation.

JAB-21822 is the potential best-in-class program for KRAS G12C inhibitors. The preliminary phase I clinical data published at the 2022 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) shows that as of April 1, 2022, a total of 72 patients with advanced solid tumors were enrolled, and efficacy was assessed for 32 NSCLC patients with KRAS G12C mutation. The overall response rate (ORR) was 56.3% (18/32) and the disease control rate (DCR) was 90.6% (29/32).

JAB-21822 has a good safety profile, and most treatment related adverse events (TRAE) were grade 1-2. Among the 72 patients, the incidences of diarrhea and vomiting were 5.6% (4/72) and 6.9% (5/72) respectively, and no gastrointestinal disorder higher than grade 2 was observed.

Currently, JAB-21822 is simultaneously undergoing clinical trials for monotherapy and combination therapy in China, the United States and Europe, including the monotherapy for NSCLC patients with KRAS G12C mutation, pancreatic ductal carcinoma and colorectal cancer; the combination therapy with EGFR monoclonal antibody to treat patients with colorectal cancer; and the combination therapy with the inhouse SHP2 inhibitor JAB-3312 to treat patients with NSCLC.

About CDE’s Breakthrough Therapy Designation

CDE’s Breakthrough Therapy Designation (BTD) is designed to expedite the clinical development of innovative drugs presenting significant clinical advantages. A breakthrough therapy must provide effective treatment for a seriously debilitating or life-threatening condition that has no effective therapy or demonstrate substantial improvement over available therapies. According to the CDE, the breakthrough therapy designation provides opportunities for more intensive CDE guidance and discussion with respect to clinical trials and development strategy, and for priority review later.

About JAB-21822

JAB-21822 is an oral, small molecule KRAS G12C inhibitor independently developed by the Company. The Company has initiated a number of Phase I/II clinical trials in China, the United States and Europe for patients harbouring KRAS G12C mutation with advanced solid tumors, including pivotal clinical trial to treat NSCLC in China; monotherapy for STK11 co-mutated NSCLC in the front-line setting; combination therapy with SHP2 inhibitor JAB-3312, anti-PD-1 monoclonal antibody and Cetuximab.

On December 15, 2022 Novavax, Inc. (Nasdaq: NVAX), a biotechnology company dedicated to developing and commercializing next-generation vaccines for serious infectious diseases, reported the pricing of an underwritten public offering to sell 6,500,000 shares of its common stock at a public offering price of $10.00 per share, or $65 million worth of shares of its common stock (Press release, Novavax, DEC 15, 2022, View Source [SID1234625331]). In connection with the common stock offering, Novavax granted the underwriters a 30-day option to purchase up to an additional 975,000 shares of its common stock at the public offering price, less underwriting discounts and commissions. The offering is expected to close on December 20, 2022, subject to customary closing conditions.

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J.P. Morgan, Jefferies and Cowen are acting as joint book-running managers and representatives of the underwriters for the common stock offering. B. Riley Securities and H.C. Wainwright & Co. are acting as co-lead managers for the common stock offering.

Concurrently with the pricing of the common stock, Novavax also announced today the pricing of its previously announced offering of $150 million aggregate principal amount of its 5.00% convertible senior notes due 2027 (the "notes") to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended. In connection with the notes offering, Novavax has granted to the initial purchasers a 30-day option to purchase up to an additional $25.25 million aggregate principal amount of the notes. The offering of the notes is expected to close on December 20, 2022, subject to customary closing conditions. The common stock offering is not contingent upon the consummation of the concurrent offering of the notes, and the concurrent offering of the notes is not contingent upon the consummation of the common stock offering.

Novavax estimates that the net proceeds from the common stock offering after deducting underwriting discounts and commissions and estimated offering expenses payable by Novavax, will be approximately $60.7 million (or approximately $69.8 million if the underwriters in that offering exercise in full their option to purchase additional shares).

Novavax may use the net proceeds from the common stock offering and, if consummated, the concurrent offering of the notes, for general corporate purposes, including but not limited to, the continued global commercial launch of Nuvaxovid, repayment or repurchase of a portion of the $325 million in outstanding principal amount of its 3.75% convertible senior unsecured notes due February 1, 2023, working capital, capital expenditures, research and development expenditures, clinical trial expenditures, repayments under its supply agreements, as well as acquisitions and other strategic purposes.

A registration statement relating to the common stock offering was filed with the Securities and Exchange Commission ("SEC") on March 11, 2020, and is effective. The common stock offering will be made only by means of a prospectus supplement and the accompanying prospectus. Before investing in the common stock offering, purchasers should read the prospectus supplement relating to and describing the terms of such public offering and the related registration statement and other documents Novavax has filed with the SEC for more complete information about Novavax and such public offering. An electronic copy of the preliminary prospectus supplement and accompanying prospectus relating to the common stock offering are available on the SEC’s website at www.sec.gov. An electronic copy of the prospectus supplement and accompanying prospectus relating to the common stock offering will be available on the SEC website at www.sec.gov, and may also be obtained, when available, from: J.P. Morgan, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388 or by email at [email protected]; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by telephone at (833) 297-2926, or by email at [email protected].

On December 15, 2022 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported that the Company plans to present at the Biotech Showcase and host institutional investor and partnering meetings at this event and a Corporate Access Event organized by LifeSci Partners (Press release, Cyclacel, DEC 15, 2022, View Source [SID1234625330]). Both in-person events are taking place January 9-11, 2023 in San Francisco, California.

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Biotech Showcase:
Spiro Rombotis, President and Chief Executive Officer, and Paul McBarron, EVP, Finance & COO, will provide an overview of the Company including clinical progress and expected milestones.

Date/Time: Tuesday January 10, 2023, at 9:30 am PT
Location: Hilton San Francisco Union Square in San Francisco; Yosemite A (Ballroom Level)
To schedule a meeting with management, investors can register on the Biotech Showcase website

LifeSci Partners Corporate Access Event:
Spiro Rombotis, President and Chief Executive Officer, and Paul McBarron, EVP, Finance & COO, will be hosting meetings with institutional investors.

Date/Time: Monday, January 9, 2023
Location: Beacon Grand Hotel, San Francisco
Please click here to register for the conference and schedule a meeting with management via the online system managed by LifeSci Partners.

On December 15, 2022 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning ("M.L.") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that it presented new positive preclinical data for its drug candidate LP-284 for Mantle Cell Lymphoma (MCL) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting (Press release, Lantern Pharma, DEC 15, 2022, View Source [SID1234625328]).

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The ASH (Free ASH Whitepaper) poster highlights new results for LP-284 from preclinical studies for MCL and initial results from investigational new drug (IND) enabling studies. LP-284 treatment was demonstrated to have significantly greater tumor growth inhibition (TGI) in mice implanted with MCL cell derived xenograft (CDX) tumors, when compared to treatment with the standard-of-care (SOC) agents Ibrutinib or Bortezomib (see Table 1).

Table 1.

Agent (Dose; Administration)

LP-284

(4 mg/kg; i.v.)

LP-284

(2 mg/kg; i.v.)

Bortezomib

(1 mg/kg; i.p.)

Ibrutinib

(50 mg/kg; p.o.)

TGI (%)

113%

63%

22%

8%

Table Legend: Tumor growth inhibition (TGI); Intravenous (i.v.); Intraperitoneal (i.p.); Oral (p.o.)

Additionally, in mouse MCL CDX tumors that had been treated and then grown resistant to either Ibrutinib or Bortezomib, subsequent LP-284 treatment of 4 mg/kg (i.v.) resulted in near complete tumor regression in the SOC resistant MCL CDX tumors (see Figure 1). These new promising results are critically important from a clinical perspective as nearly all MCL patients eventually relapse from Ibrutinib and Bortezomib treatment.

New in vitro data was also presented that identified a potential mechanism of LP-284’s anti-tumor activity in MCL. LP-284 treatment of MCL cell lines significantly down-regulated key cancer promoting genes and pathways, including the onco-fusion gene CCND1 and genes in the MYC pathway. Combined, these new in vitro and in vivo preclinical data for LP-284 strongly support its anti-tumor activity in MCL over current SOC agents and its continued advancement towards a Phase 1 clinical trial.

"This compelling pre-clinical efficacy and tumor response data, in both new lymphomas and those that had become resistant to standard of care agents, is an exciting advancement for LP-284 in hematological cancers and positions Lantern to advance our discussions with biopharma companies for partnering and collaborative development opportunities," stated Panna Sharma, Lantern’s CEO and President. "Even with the vanguard of new CAR T-cell therapy approaches in B-cell cancers, there is a critical need for improved options for B-cell cancer patients that don’t qualify for, have access to, or can’t afford CAR T-cell therapy," continued Sharma.

The ASH (Free ASH Whitepaper) poster also shows initial results from the large animal non-GLP toxicology portion of the IND enabling studies for LP-284, where the no observed adverse effect level (NOAEL) of LP-284 was determined to be 0.3 mg/kg/dose. Establishment of the NOAEL will facilitate the completion of IND enabling studies, which Lantern is anticipating in Q1 of 2023, followed by an anticipated launch of a first in human Phase 1 clinical trial later in 2023.

A full version of the poster presentation can be found on Lantern’s website.

About LP-284:

LP-284 is a novel small molecule and DNA damaging agent being developed by Lantern for the treatment of several non-Hodgkin’s lymphomas (NHL) including MCL and double hit lymphoma (DHL). Lantern’s LP-284 program has been accelerated and de-risked using A.I. insights and biological modeling powered by RADR. Lantern has been able to advance LP-284 from initial RADR insights regarding anti-cancer activity and potential mechanisms of action in hematological cancers, to selection of specific subtypes of lymphomas with superior response, to late stage IND enabling studies and initial design of first in human clinical trials in less than 2 years.