On November 14, 2022 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of targeted immunotherapies for cancer and infectious disease, reported that it will discuss its financial results for the quarter ended September 30, 2022 and provide a business update on its conference call (Press release, PDS Biotechnology, NOV 14, 2022, View Source [SID1234623932]).

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Recent Business Highlights:

PDS0101 Lead Drug Candidate
VERSATILE-002 Phase 2 Clinical Trial
Hosted a key opinion leader roundtable discussion on current treatment of head and neck cancer, and how PDS0101 might fit into the treatment paradigm.
Announced a successful end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA), allowing progression to a registrational trial for VERSATILE-002.
IMMUNOCERV Phase 2 Clinical Trial
Presented preliminary data on the clinical efficacy and safety of the combination of PDS0101 and chemoradiotherapy, as well as immunological correlates in the IMMUNOCERV Phase 2 trial being conducted at The University of Texas MD Anderson Cancer Center in locally, advanced cervical cancer at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (SITC) (Free SITC Whitepaper) 2022.
NCI-led Triple Combination Phase 2 Clinical Trial
Presented data on immunological correlates associated with clinical benefit in patients with HPV-positive checkpoint inhibitor (CPI) refractory cancer treated with the PDS0101-based triple combination in the National Cancer Institute (NCI)-led Phase 2 clinical trial at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (SITC) (Free SITC Whitepaper) 2022.
Reported expanded interim data for the Phase 2 PDS0101 based triple combination trial led by the NCI targeting advanced HPV-positive cancers.
Announced completion of recruitment into the NCI-led PDS0101-based triple combination Phase 2 trial, and also reported selection of the CPI refractory arm as the preferred patient group to target in a registrational study with the triple combination.
PDS0102 and PDS0103 Drug Candidates
Presented preclinical data on both PDS0102 and PDS0103, demonstrating the versatility of the Versamune platform and generation of TARP and MUC1 specific polyfunctional CD8+ T cells presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Special Conference: Tumor Immunology and Immunotherapy 2022.
PDS0202 Universal Flu Candidate
Presented data from the preclinical universal flu vaccine program at the American Society of Virology meeting, demonstrating the potential ability of PDS0202 to neutralize multiple strains of influenza in animals.
Financing
Entered into a venture loan and security agreement with Horizon Technology Finance Corporation, which provides PDS Biotech with up to $35 million in term loans.
"The third quarter has been monumental for PDS Biotech, and we continue to make strides towards commercialization of our lead candidate, PDS0101," stated Dr. Frank Bedu-Addo, President and Chief Executive Officer of PDS Biotech. We’ve remained focused on progressing our four Phase 2 clinical programs, most recently, announcing data from our IMMUNOCERV trial in locally, advanced cervical cancer. 100% (9/9) of patients had a clinical response with tumor shrinkage of over 60% at the midpoint evaluation, and 89% (8/9) of patients had a complete response with no evidence of disease at day 170, when treated with a combination of PDS0101 and chemotherapy. Furthermore, we released expanded interim data from our NCI-led PDS0101-based triple combination trial demonstrating 66% (19/29) survival at median follow up of 16 months in checkpoint inhibitor refractory HPV-positive cancer patients that appears to show signs of clinical efficacy, durability, and safety, consistent with the data presented at the American Society for Clinical Oncology 2022. And, with VERSATILE-002 in which PDS0101 is combined with KEYTRUDA, we are preparing for a registrational trial after our successful end-of-Phase 2 meeting with the FDA. To date, we have presented PDS0101 Phase 2 efficacy data in over 60 patients and safety data in over 100 patients."

Matthew Hill, Chief Financial Officer of PDS Biotech, stated, "We are excited about the progress we have made in our development programs, and we have strengthened the balance sheet to support our ongoing efforts. This August, we increased our cash position by entering into a loan agreement with Horizon Technology Finance Corporation, where we received an initial tranche of $25 million in term loans. This financing provides PDS Biotech with the financial resources and runway needed to prepare for a registrational trial for our lead candidate, PDS0101, and to advance our preclinical pipeline."

Third Quarter 2022 Financial Results
Net loss for the three months ended September 30, 2022 was approximately $7.4 million, or $0.26 per basic share and diluted share, compared to a net loss of approximately $7.0 million, or $0.24 per basic and diluted share, for the three months ended September 30, 2021. The higher net loss reported for the three months ended September 2022 is primarily due to additional costs for expansion of the Company’s research and development, including costs associated with our ongoing clinical trials and additional general and administrative costs.

Research and development expenses increased to $4.4 million for the three months ended September 30, 2022 from $3.7 million for the three months ended September 30, 2021. The increase of $0.7 million in 2022 was primarily attributable to an increase of $0.2 million in clinical study and research costs, $0.3 million in personnel costs and $0.4 million in manufacturing services partially offset by a decrease of $0.2 million in professional fees and facilities.

General and administrative expenses decreased to $2.9 million for the three months ended September 30, 2022 from $3.3 million for the three months ended September 30, 2021. The decrease of $0.4 million is primarily attributable to a decrease of $0.5 million in personnel an increase of $0.2 million in professional fees partially offset by a decrease of $0.1 million in facilities costs.

Total operating expenses were approximately $7.3 million for the three months ended September 30, 2022, from approximately $7.0 million for the three months ended September 30, 2021.

PDS Biotech’s cash balance as of September 30, 2022 was approximately $71.6 million.

Conference Call and Webcast
The conference call is scheduled to begin at 8:00 AM EST today, November 14, 2022. Participants should dial 877-407-3088 (United States) or 201-389-0927 (International) and reference conference ID 13733006. To access the webcast, please use the following link. The event will be archived in the investor relations section of PDS Biotech’s website for six months.

About PDS0101
PDS Biotech’s lead candidate, PDS0101, combines the utility of the Versamune platform with targeted antigens in HPV-positive cancers. In partnership with Merck & Co., PDS Biotech is evaluating a combination of PDS0101 and KEYTRUDA in a Phase 2 study in first-line treatment of recurrent or metastatic head and neck cancer, and also in second line treatment of recurrent or metastatic head and neck cancer in patients who have failed prior checkpoint inhibitor therapy. A Phase 2 clinical study is also being conducted in both second- and third-line treatment of multiple advanced HPV-positive cancers in partnership with the National Cancer Institute (NCI). A third Phase 2 clinical trial in first line treatment of locally advanced cervical cancer is being performed with The University of Texas, MD Anderson Cancer Center. A final Phase 2 clinical trial of PDS0101 monotherapy in first line treatment of newly diagnosed patients HPV16-positive head and neck cancer patients is being conducted at the Mayo Clinic.

KEYTRUDA is a registered trademark of Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On November 14, 2022 Lumos Pharma, Inc. (NASDAQ:LUMO), a clinical-stage biopharmaceutical company focused on therapeutics for rare diseases, reported that interim results met expectations for its Phase 2 OraGrowtH210 Trial and Phase 2 Pharmacokinetic/Pharmacodynamic (PK/PD) OraGrowtH212 Trial evaluating oral LUM-201 for subjects with moderate (idiopathic) pediatric growth hormone deficiency (PGHD) who screened PEM-positive utilizing Lumos’s predictive enrichment marker (PEM) strategy (Press release, Lumos Pharma, NOV 14, 2022, View Source [SID1234623931]). Lumos also announced its financial results for the quarter ended September 30, 2022.

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"With the interim readout from our OraGrowtH210 and OraGrowtH212 trials announced today, we look forward to continuing to advance our clinical program and planning for our pivotal Phase 3 trial for potentially the first oral therapeutic for PGHD," said Rick Hawkins, Chairman and CEO of Lumos Pharma. "In the 1.6 mg/kg/day LUM-201 arm in the OraGrowtH210 study, we observed mean annualized height velocity of 8.6 cm/yr, in line with 8.3 cm/yr expected based on growth on rhGH for moderate PGHD subjects observed in multiple large datasets. We look forward to building on this initial data and expect to report primary outcome results from both OraGrowtH trials in the second half of 2023. Additionally, our collaboration with Mass General on an investigator sponsored trial evaluating LUM-201 in NAFLD continues, and the trial has dosed its first subject and continues to enroll."

Recent Highlights

Interim analyses for Phase 2 OraGrowtH210 and PK/PD OraGrowtH212 Trials met expectations. Interim analysis for Phase 2 OraGrowtH210 Trial demonstrated that the 1.6 mg/kg/day LUM-201 dose produced a mean annualized height velocity (AHV) of 8.6 cm/yr at six months on treatment for moderate (idiopathic) PGHD subjects. This met the expected AHV of 8.3 cm/yr observed for moderate naive-to-treatment PGHD subjects on rhGH at 12 months observed in Eli Lilly’s large Phase 4 GeNeSIS1 dataset and comparable findings from other large historical datasets.2,3 In addition, interim data from both OraGrowtH210 and OraGrowtH212 Trials demonstrated durability of LUM-201 response out to 12 months. The rhGH control arm produced an AHV of 11.05 cm at six months, an unexpected growth response in this moderate PGHD population. This higher than anticipated AHV in the rhGH arm was likely due both to the presence of a growth outlier and to imbalances in several baseline characteristics for this arm that are well documented in the published literature as predictors of greater growth response to rhGH. We believe LUM-201 will demonstrate a favorable safety profile as our interim data from both OraGrowtH trials show comparable safety and tolerability to the rhGH subjects in the trials. Interim data from both OraGrowtH trials support the selection of the 1.6 mg/kg/day LUM-201 dose for a pivotal Phase 3 trial. For a link to the Company’s conference call and presentation of the data refer to the Company’s website at Investor Relations – Events and Presentations.

Enrollment for the OraGrowtH210 Trial is now at ~80%. The primary outcome data on 80 subjects from OraGrowtH210 Trial and up to 24 subjects from our OraGrowtH212 Trial continues to be anticipated in the second half of 2023.

Enrollment Initiated in Massachusetts General Investigator-Initiated Trial evaluating LUM-201 in NAFLD. As previously announced, we entered into a clinical collaboration with Dr. Laura Dichtel and Massachusetts General Hospital to explore the potential of LUM-201 in Nonalcoholic Fatty Liver Disease (NAFLD) in an investigator sponsored pilot study. Enrollment in the trial has begun, and the first subject has been dosed. While we remain focused on our core LUM-201 program in PGHD, we are pleased to support Mass General’s exploration of LUM-201’s potential in this indication, a condition estimated to be prevalent in approximately 25% of adults worldwide. NAFLD can often advance to the more serious liver disease non-alcoholic steatohepatitis (NASH) with fibrosis, and NASH-associated liver failure is one of the leading causes of liver transplants in the United States.
1 Blum et al JES 2021, 2 Lechuga-Sancho et al JPEM 2009, 3 Ranke et al JCEM 2010,

Financial Results for the Quarter Ended September 30, 2022

Cash Position – Lumos Pharma ended the quarter on September 30, 2022 with cash and cash equivalents totaling $73.7 million compared to $94.8 million on December 31, 2021. The Company expects cash use of approximately $8.5 to $9.5 million in the fourth quarter of 2022. Cash on hand as of September 30, 2022 is expected to support operations into the second quarter of 2024, inclusive of the primary outcome data readout from OraGrowtH210 and OraGrowtH212 Trials anticipated in the second half of 2023.
R&D Expenses – Research and development expenses were $4.1 million for the quarter ended September 30, 2022, compared to $4.1 million for the same period in 2021, primarily due to an increase of $0.3 million in personnel-related expenses and $0.1 million in consulting expenses, offset by a decrease of $0.4 million in clinical trial and contract manufacturing expenses.
G&A Expenses – General and administrative expenses were $3.9 million for the quarter ended September 30, 2022, an increase compared to $3.4 million for the same period in 2021, primarily due to increases of $0.3 million in royalty expenses, $0.2 million in consulting expenses and $0.1 million in travel-related expenses, offset by a decrease of $0.1 million in other miscellaneous expenses.
Net Loss – The net loss for the quarter ended September 30, 2022 was $7.3 million compared to net loss of $7.5 million for the same period in 2021.
Lumos Pharma ended the third quarter 2022 with 8,375,271 shares outstanding.
About Lumos Pharma’s Clinical Trials

Phase 2 OraGrowtH210 Trial of Oral LUM-201 in PGHD

The OraGrowtH210 Trial is a multi-site, global trial evaluating orally administered LUM-201 at three dose levels (0.8, 1.6, 3.2 mg/kg/day) against a standard dose of injectable rhGH in approximately 80 subjects diagnosed with idiopathic (moderate) PGHD, which is less severe than organic PGHD. The objective of this trial is to identify the optimal dose of LUM-201 to be used in a Phase 3 registration trial, based on annualized height velocity from a 6-month dataset, and to prospectively confirm the preliminary validation of our Predictive Enrichment Marker (PEM) strategy. The interim analysis demonstrated that LUM-201 in the 1.6 mg/kg/day arm met expectations at six months of treatment with an AHV of 8.6 cm as compared to the AHV of 8.3 cm observed in the PEM-positive moderate naive-to-treatment PGHD subjects for 12 months on rhGH as derived from the large 20-year Phase 4 Eli Lilly GeNeSIS database. The complete set of six-month, primary outcome data for 80 subjects is anticipated in the second half of 2023. Subjects will be treated for up to 24 months.

OraGrowtH212 Trial Evaluating PK/PD and Pulsatility of Oral LUM-201 in PGHD

The OraGrowtH212 Trial is a single site, open-label trial evaluating the pharmacokinetic (PK) and pharmacodynamic (PD) effects of oral LUM-201 in up to 24 PGHD subjects at two dose levels, 1.6 and 3.2 mg/kg/day. The primary objective of the OraGrowtH212 Trial is to confirm prior clinical data demonstrating the amplified pulsatile release of endogenous growth hormone from LUM-201 therapy, contributes to its efficacy in PGHD. The primary endpoint for this trial is six months of PK/PD (pulsatility) and height velocity data in up to 24 subjects. Subjects will be allowed to remain on treatment until they reach their near-adult height. Primary data readout in up to 24 subjects is anticipated in the second half of 2023.

Switch Study, OraGrowtH213 Trial, Evaluating LUM-201 in OraGrowtH210 Subjects Previously on rhGH

The OraGrowtH213 Trial is an open-label, multi-center, Phase 2 study evaluating the growth effects and safety of LUM-201 following 12 months of daily rhGH in up to 20 idiopathic PGHD subjects who have completed the OraGrowtH210 Trial. Subjects will be administered LUM-201 at a dose level of 3.2 mg/kg/day for up to 12 months.

Lumos Pharma Collaboration with Massachusetts General Hospital Evaluating LUM-201 in NAFLD

Lumos Pharma has entered a collaboration with Massachusetts General Hospital (MGH) to evaluate LUM-201 in subjects with nonalcoholic fatty liver disease (NAFLD). GH is a critical stimulator of lipolysis, and shows anti-inflammatory effects, and preclinical data suggest that amplifying GH secretion has the potential to reduce hepatic steatosis and prevent NAFLD progression. Interestingly, enhancing the natural pulsatile release of GH has been shown clinically in short-term studies to be more efficacious in inducing lipolysis than continuous infusions of GH. This MGH investigator-initiated trial is a single-site, 6-month, open-label pilot study of daily oral LUM-201 in adults with NAFLD. The trial will evaluate a dose of 25 mg/day of LUM-201 in ten subjects with NAFLD and relative IGF-1 deficiency. The primary endpoints will be to determine the reduction in liver lipid content, inflammation, and fibrosis in these subjects administered LUM-201 compared to each subject’s baseline.

On November 14, 2022 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported acceleration of opaganib’s development program for protection against radiation injury and cancer radiotherapy (Press release, RedHill Biopharma, NOV 14, 2022, View Source [SID1234623930]). A recent publication in the International Journal of Molecular Sciences, entitled "Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy", describes the collective results of eight U.S. government-funded in vivo studies by RedHill and Apogee Biotechnology Corporation ("Apogee"), as well as additional experiments, establishing opaganib’s1 potential nuclear radiation protection capabilities2.

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The publication highlights observations from numerous studies undertaken in both protection against radiation toxicity and cancer radiotherapy settings. In the relevant study models, opaganib was associated with protection of normal tissue, including gastrointestinal, from radiation damage due to ionizing radiation exposure or cancer radiotherapy, as well as improvement of antitumor activity, response to chemoradiation, and enhancement of tolerability and survival. Additional independent studies demonstrate the radioprotective capacity of opaganib in bone marrow, with opaganib showing enhanced survival in mice which were irradiated with both lethal and half-lethal whole-body radiation3.

"Subject to further alignment with FDA, we intend to follow the Animal Rule path to approval for opaganib, based on prior FDA guidance specific to opaganib for the intended indication. Development for medical countermeasures may follow the Animal Rule, with pivotal animal model studies of efficacy applicable when human clinical trials are not ethical or feasible. In addition, we intend to seek an expedited development timeframe and eligibility for a Medical Counter Measure Priority Review Voucher. Amid the growing awareness of the need for material threat medical countermeasures and the positive observations seen in these in vivo gastrointestinal focused radiation toxicity and cancer radiotherapy studies, along with external data indicating potential radioprotective capacity of opaganib in bone marrow, we have accelerated our development plans to further test opaganib as a protective agent against nuclear radiation toxicity. We have recently initiated a new study to assess protective effects of opaganib on radiation-induced hematologic and renal toxicity, with our partner Apogee. Another meeting with the FDA is scheduled to seek further guidance on the path to homeland security medical countermeasure approval. Discussions with multiple government agencies in the U.S. and internationally, regarding funding and other governmental support, have been initiated," said Gilead Raday, Chief Operating Officer and Head of R&D at RedHill. "Importantly, opaganib has demonstrated its safety and tolerability profile in more than 470 people in studies in other indications as well as expanded access use. As an oral, small molecule pill that is highly stable with a greater than five-year shelf-life, opaganib is easy to administer and distribute, supporting potential central countermeasures stockpiling by governments."
2

Mitigation of radiation toxicity is an area of governmental concern. A key priority for US government research efforts is focused on finding long shelf-life and easy to distribute and administer drugs for potential inclusion in the Strategic National Stockpile. Such drugs, to be used in mass casualty nuclear radiation incidents involving improvised nuclear or radiological dispersal devices, should have broad-acting protective capability, be able to be administered 24 hours or later after radiation exposure, be safe and be easy to distribute to large numbers of people needing treatment for the acute effects of high dose, whole-body radiation exposure.

Currently, to the best of the Company’s knowledge, only four FDA-approved medical countermeasure therapies are available. Three of these options are limited to effects caused by a small number of specific radioactive materials or to specific parts of the body. Potassium iodide (iodine pills) is intended to be used to protect against thyroid damage from the release of radioiodine. It works by preventing the thyroid from taking up radioactive iodine but seems to offer no protection to the rest of the body from irradiation and is of limited benefit unless given immediately upon exposure. The other two, Prussian Blue and DTPA (diethylenetriamine pentaacetate) provide protection by limiting the half-life in the body of specific materials: radioactive cesium and thallium, in the case of Prussian Blue, and radioactive plutonium, americium, and curium, in the case of DTPA. The fourth option, filgrastim, is intended for acute radiation syndrome resulting from high-dose radiation. Filgrastim does not seem to protect the body against the radiation itself and works by stimulating the creation of new white blood cells to protect the body from infections, which the body can no longer do in the presence of radiation-induced bone marrow destruction – as long as there are viable stem cells to stimulate.

We believe that opaganib’s protection would not be limited to specific radioactive materials or individual parts of the body. Much of the damage caused by radiation exposure is caused by inflammation secondary to the effects of ionizing radiation itself – known as Acute Radiation Syndrome. Opaganib, a sphingosine kinase-2 (SK2) inhibitor, is thought to exert its protective effects via an anti-inflammatory mechanism of action involving ceramide elevation and reduction of sphingosine 1-phosphate (S1P) in human cells – suppressing inflammatory damage to normal tissue and thus suppressing toxicity from unintended ionizing radiation exposure. It has also been reported in the literature that inhibition of sphingosine kinase 2 promotes the viability and robustness of hematopoietic stem cells, even in the face of radiation damage, supporting increased survival.

3
Protection against radiation toxicity studies with opaganib funded by U.S. government – summary of results:

Effect of opaganib on the lethality of TBI (Total Body Irradiation) in C57BL/6 mice
Vehicle-treated mice had pronounced symptoms indicative of severe GI damage, and all animals had to be euthanized within 14 days of radiation exposure. In contrast, protection was observed in the opaganib-treated group, in which 71% of the mice survived indefinitely.

Accumulation and pharmacodynamics of opaganib in mouse small intestine
In vehicle-treated mice, TNFα expression in the small intestines was observed to be up-regulated as early as 1 hour after Total Body Irradiation (TBI) and remained highly elevated for at least 26 hours. In contrast, pretreatment with opaganib was observed to not only block the induction of TNFα by TBI but also to reduce tissue TNFα levels below the baseline level indicating prolonged biodistribution of opaganib into the small intestine at sufficient levels to inhibit SK2 and suppress radiation-induced inflammation.

Effects of opaganib on GI damage following TBI
Post-radiation decreases in villus height (villi are a critical component of the intestines ability to absorb nutrients and indicative of intestinal health) were observed in the vehicle-treated animals compared with non-irradiated controls. In contrast, villus height was maintained in the opaganib-treated mice. Additionally, while there was evidence of cell depletion after 10 days in all groups, there were significantly more cells present at 4 days after irradiation in the opaganib-treated mice compared to vehicle controls (p<0.001) with this difference between treatments nearly resolving by Day 10.

Effect of opaganib on the lethality of partially shielded irradiation in C57BL/6 mice
In multiple scenarios, utilizing partial bone marrow shielding, involving different levels of irradiation and with different dosing regimens, opaganib was observed to reduce mortality, with the greatest improvement seen when opaganib was given both before and after irradiation, reducing mortality from 82% down to 4% (p<0.001) in the mice given the highest dose of radiation, 16 Gray (Gy).

Cancer radiotherapy studies with opaganib funded by U.S. government – summary of results:

In vitro effects of opaganib on cell radiosensitivity
Opaganib appeared to provide protection from IR-induced cell death, with observations showing the level of radiation need to kill 50% and 90% of intestinal epithelial cells increasing from 5.56 and 12.16 Gy respectively up to 6.46 and 13.2 Gy, respectively. Furthermore, opaganib was observed to increase the killing of transformed pancreatic cancer cells by radiation, particularly at the high dose of 15 Gy (p<0.05).

In vivo effects of combination of opaganib with radiation on tumor growth (multiple cancer-types):
Pancreatic cancer model: Treatment with either TBI alone or opaganib alone substantially reduced tumor growth (p<0.05 and p<0.001, respectively). Treatment with opaganib in combination with TBI was associated with significantly reduced tumor growth compared to the control group or to the TBI alone group (p<0.01 for each comparison) but was not significantly different from opaganib alone because of the strong antitumor activity of the drug in this model. Importantly, treatment with opaganib did not protect tumors from radiation treatment.

Melanoma and E0771 breast cancer model: Opaganib plus TBI was observed to have equal or better antitumor activity than TBI alone. Again, opaganib was not associated with a diminished tumor response to fractionated radiation treatment and increased weight loss from radiation treatment was not observed.

Head & neck cancer model: Treatment with opaganib alone was observed to slightly reduce tumor growth, while TBI + cisplatin was observed to substantially reduce tumor growth as compared to the control (vehicle) group (p<0.001). Treatment with opaganib in combination with TBI + cisplatin was associated with the greatest reduction in tumor growth and such treatment group had significantly better observations than TBI + cisplatin on Day 21 and after (p<0.02). Again, opaganib was not associated with diminished tumor response or increased weight loss.
4

About Opaganib (ABC294640)
Opaganib a new chemical entity, is an orally administered, first-in-class proprietary selective inhibitor of sphingosine kinase-2 (SK2) with suggested anti-inflammatory, anticancer, radioprotective and antiviral activity.

Opaganib is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SK2, DES1 and GCS).

In an oncology & radiological setting, opaganib has been observed to elevate ceramide and reduces sphingosine 1-phosphate (S1P) in cells, conditions that increase the antitumor efficacy of radiation while concomitantly suppressing inflammatory damage to normal tissue, leading to the potential to suppress toxicity from unintended ionizing radiation (IR) exposure and improve patient response to chemoradiation. Opaganib has received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma and is being evaluated in a Phase 2a study in advanced cholangiocarcinoma. Patient accrual, treatment and analysis in a prostate cancer study is ongoing. Opaganib has a Phase 1 chemoradiotherapy study protocol ready for IND submission.

Opaganib has demonstrated broad-acting, host-directed, antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A. Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Data from the opaganib global Phase 2/3 study has been submitted for peer review and recently published in medRxiv.

Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications.

On November 14, 2022 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the third quarter ended September 30, 2022 and provided a business update on recent corporate and regulatory developments (Press release, Protalix, NOV 14, 2022, View Source [SID1234623929]).

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"We are happy we have reached a significant milestone for our company with the recent BLA resubmission to the FDA," said Dror Bashan, Protalix’s President and Chief Executive Officer. "We believe PRX-102, if approved, has the potential to significantly impact patients living with this rare, life-threatening genetic disease. As we approach potential approval and commercialization of PRX-102, we affirm our dedication to our mission of bringing new medicines to patients with serious diseases. We are grateful to our team members and external partners for their continued commitment to this program."

2022 Third Quarter and Recent Business Highlights

Regulatory Updates

●On November 9, 2022, the Company, together with its development and commercialization partner for PRX-102, Chiesi Farmaceutici S.p.A. ("Chiesi"), resubmitted a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) for PRX-102 (pegunigalsidase alfa) for the treatment of adult patients with Fabry disease. The BLA re-submission included the final two year analyses of our phase III BALANCE clinical trial, which analyses were completed in July 2022, and long-term data from our open-label extension study of PRX-102 in adult patients treated with a 2 mg/kg every four weeks dosage of PRX 102. The initial BLA included a comprehensive set of preclinical, clinical and manufacturing data compiled from our completed phase I/II clinical trial of PRX 102, including the related extension study, interim clinical data from our phase III BRIDGE clinical trial and safety data from our on-going clinical studies of PRX 102 in adult patients receiving 1 mg/kg every two weeks.
Third Quarter 2022 Financial Highlights

●The Company recorded revenues from selling goods of $8.8 million during the three months ended September 30, 2022, an increase of $4.3 million, or 96%, compared to revenues of $4.5 million for the three months ended September 30, 2021. An increase of $3.4 million in sales to Pfizer Inc., resulting from timing differences, and an increase of $2.4 million in sales to Chiesi was partially offset by a decrease of $1.5 million in sales to Brazil resulting from timing differences.
●Revenue from licenses and R&D services for the three months ended September 30, 2022 were $5.4 million, a decrease of $2.1 million, or 28%, compared to revenues of $7.5 million for the three months ended September 30, 2021. Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements.
●Cost of goods sold was $7.1 million for the three months ended September 30, 2022, an increase of $3.4 million, or 91%, from cost of goods sold of $3.7 million for the three months ended September 30, 2021. The increase in cost of goods sold was primarily the result of the increase in sales of goods.
●For the three months ended September 30, 2022, our total research and development expenses were approximately $7.4 million comprised of approximately $4.9 million in subcontractor-related expenses, approximately $1.7 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.6 million of other expenses. For the three months ended September 30, 2021, our total research and development expenses were approximately $7.3 million comprised of approximately $4.8 million in subcontractor-related expenses, approximately $1.6 million of salary and related expenses, approximately $0.1 million of materials-related expenses and approximately $0.8 million of other expenses. Total increase in research and developments expenses was $0.1 million, or 1%, for the three months ended September 30, 2022 compared to the three months ended September 30, 2021.
●Selling, general and administrative expenses were $2.8 million for the three months ended September 30, 2022, a decrease of $0.2 million, or 7%, compared to $3.0 million for the three months ended September 30, 2021. The decrease was primarily due to a decrease in salary related and selling costs.
●Financial expenses, net were $0.4 million for the three months ended September 30, 2022, compared to $2.3 million for the three months ended September 30, 2021. The decrease resulted primarily from lower interest and debt amortization costs due to a decrease in our outstanding notes from an aggregate principal amount of $57.92 million of 2021 Notes to an aggregate principal amount of $28.75 million of 2024 Notes, and an increase in the exchange rate of New Israeli Shekels for U.S. Dollars over the period.
●Cash, cash equivalents and short-term bank deposits were approximately $20.8 million at September 30, 2022.
●Net loss for the three months ended September 30, 2022 was approximately $3.6 million, or $0.07 per share, basic and diluted, compared to a net loss of approximately $4.2 million, or $0.09 per share, basic and diluted, for the same period in 2021.
Conference Call and Webcast Information

The Company will host a conference call today, November 14, 2022, at 8:30 a.m. Eastern Standard Time, to review the corporate and regulatory developments, which will also be available by webcast. To participate in the conference call, please dial the following numbers prior to the start of the call:

Please access the websites at least 15 minutes ahead of the conference to register, download and install any necessary audio software.

The conference call will be available for replay for two weeks on the Events Calendar of the Investors section of the Company’s website, at the above link.

On November 14, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported financial results for the third quarter ended September 30, 2022 (Press release, Cogent Biosciences, NOV 14, 2022, View Source [SID1234623928]).

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"We are excited to announce the initiation of our Phase 3 PEAK trial in imatinib-resistant, second line GIST patients and look forward to presenting an update from our Phase 2 APEX trial in ASM patients in an oral presentation at ASH (Free ASH Whitepaper) 2022," said Andrew Robbins, President and CEO of Cogent Biosciences. "Our team has made tremendous progress this year, advancing our three bezuclastinib clinical trials, PEAK, APEX, and SUMMIT, recently presenting new data on our novel FGFR2 and ErbB2 selective programs, and delivering an optimized formulation of bezuclastinib which will significantly improve the patient experience."

Recent Business Highlights

Initiated the randomized portion of PEAK, a global Phase 3 clinical trial in GIST patients who have progressed following imatinib therapy. The trial is designed to explore the efficacy of bezuclastinib in combination with sunitinib compared to sunitinib alone.
The experimental arm of the PEAK trial includes a 600 mg daily dose of an optimized formulation of bezuclastinib, supplied as 75 mg tablets, which in the lead-in portion of the study demonstrated clinical exposures equivalent to the 1,000 mg daily dose of the original formulation used in the GIST Phase 1/2 clinical trial.

Presented preclinical data at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) annual meeting on a next-generation fibroblast growth factor receptor 2 (FGFR2) program, which retains potency across all primary, gatekeeper and molecular brake resistance mutations, including N549K and V564I, while sparing FGFR1 inhibition. This program remains on track for IND in 2023, with IND-enabling activities to commence early next year.

Presented preclinical data at ENA on a novel ErbB2 mutant selective program which demonstrates robust cellular inhibition of all key resistance and primary driver mutations, including L755S, V842I and S310F/Y, while sparing wild type EGFR target engagement.
Upcoming Milestones

Present updated clinical data from APEX, a global, multicenter Phase 2 clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) in an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Sunday, December 11, 2022. The presentation will include measures of clinical activity, including initial patient response assessment, in addition to pharmacokinetic and safety data. Cogent will host an investor webcast on December 12, 2022 at 8:00 am ET to discuss these data.
Preliminary Safety and Efficacy from Apex, a Phase 2 Study of Bezuclastinib (CGT9486), a Novel, Highly Selective, Potent KIT D816V Tyrosine Kinase Inhibitor, in Adults with Advanced Systemic Mastocytosis (AdvSM)
Presenter: Daniel DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute
Present initial safety and pharmacokinetic data from the PEAK lead-in study at the Connective Tissue Oncology Society (CTOS) annual meeting, November 16-19, 2022.
Peak Study: A Phase 3 Randomized, Open-label, Multicenter Clinical Study of Bezuclastinib (CGT9486) and Sunitinib Versus Sunitinib in Patients with Gastrointestinal Stromal Tumors
Presenter: Andrew J. Wagner, MD, Ph.D., Associate Chief Medical Officer at the Dana Farber Cancer Institute
Present initial clinical efficacy results from refractory GIST patients receiving bezuclastinib plus sunitinib in the PEAK lead-in study during first half of 2023.

Present initial clinical data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial of bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM), now in the second half of 2023. Based on the exciting performance of bezuclastinib’s optimized formulation in the PEAK lead-in trial, as well as in a separate healthy volunteer study, the SUMMIT trial protocol will be amended to allow for the optimized formulation to be introduced during the dose exploration phase.
Begin IND enabling studies for a potentially best-in-class, FGFR1-sparing, pan-FGFR2 mutation tyrosine kinase inhibitor in early 2023. This program is Cogent’s first internally developed research program and has been designed to overcome the clinical challenges of emergent FGFR2 treatment resistance, including the gatekeeper and molecular brake mutations that are the most common drivers of resistance, as well as off-target FGFR1 related adverse events that may limit the use of currently available and development stage FGFR2 tyrosine kinase inhibitors.
Third Quarter 2022 Financial Results

Cash Position: As of September 30, 2022, cash, cash equivalents and marketable securities were $289.1 million, as compared to $325.6 million as of June 30, 2022. The company believes that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2025. During the third quarter of 2022 Cogent incurred one-time cash payments of $8.6 million mainly related to the build-out and equipment costs associated with its newly-constructed Research Lab in Boulder, CO.

R&D Expenses: Research and development expenses were $29.9 million for the third quarter of 2022 as compared to $14.8 million for the third quarter of 2021. R&D expenses include non-cash stock compensation expense of $2.1 million for the third quarter of 2022 compared to $1.4 million for the third quarter of 2021. Additional increases resulted from costs associated with the APEX, SUMMIT and PEAK clinical trials as well as costs related to expanding the Cogent Research Team, which was formed in the second quarter of 2021.

G&A Expenses: General and administrative expenses were $6.9 million for the third quarter of 2022 as compared to $5.0 million for the third quarter of 2021. G&A expenses include non-cash stock compensation expense of $2.6 million for the third quarter of 2022 compared to $2.0 million for the third quarter of 2021.

Net Loss: Net loss was $35.1 million for the third quarter of 2022 as compared to a net loss of $19.1 million for the same period of 2021.