On November 1, 2021 Lantern Pharma (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that its proprietary A.I. platform RADR has exceeded 10.4 billion datapoints(Press release, Lantern Pharma, NOV 1, 2021, View Source [SID1234594650]). RADR is Lantern’s proprietary integrated A.I. platform for large-scale biomarker and drug-tumor interaction data analytics that leverages machine-learning. RADR is used to provide mechanistic insights about drug-tumor interactions, predict the potential response of cancer types and subtypes to existing drugs and drug candidates, and uncover patient groups that may respond to potential therapies being developed by Lantern and its collaborators.

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RADR is also being used to: (1) help define and develop combination strategies involving drugs in development by Lantern and existing drugs that are approved for a range of oncology indications; (2) guide the prioritization of potential indications for development; and (3) identify potential new drug candidates to in-license and develop.

The increase to 10.4 billion datapoints was also accompanied by other significant improvements in the functionality, feature set and further automation of RADR, which are intended to help scale the A.I. platform’s drug development capabilities. The significant increase in the number of drug-tumor interaction data sets and cancers sub-types covered by RADR includes new data from collaborations in glioblastoma multiforme (GBM) and pancreatic cancer and data from transcriptome, genome and methylome data-sets in blood, bladder and other rare cancers being considered for future development or have limited therapeutic options.

Panna Sharma, CEO and President of Lantern Pharma, stated, "Our team has been well ahead of schedule in the growth of our platform, and RADR has now surpassed 10.4 billion data points covering more cancer sub-types, which further advances our goal of building the most complete and powerful A.I. platform for precision oncology drug development. Additionally, the new data will drive insights and potential drug-candidate innovations faster and into areas of cancer that have remained untouched or intractable."

Corresponding with this growth in datapoints, the Company has also focused resources and technology development on the growth and improvements to the library of algorithms designed specifically to help solve challenging data and correlation problems for cancer drug development. By using an ensemble-based approach in applying the library of algorithms to statistical, correlative and inferential problems related to drug-tumor interaction, RADR can rapidly analyze large amounts of complex data and predict with high accuracy how both tumors and patients will respond to drugs and drug candidates. RADR’s ability to rapidly sift through large amounts of curated and complex datasets is key in predicting the probability of a tumor or a patient group in responding to a cancer treatment. Additionally, the RADR platform evolves as new datasets are added, which improves and sharpens the insights generated from the algorithms. Lantern plans on continuing further RADR expansion by incorporating and curating additional datasets from proprietary studies and public data sources and further automating the evolution of its library of algorithms. Additionally, the Company will be augmenting the 10.4 billion datapoints with additional data from immuno-oncology related studies and clinical trials, including antigen, immune-response and protein data that it believes will enable a potentially more robust and more powerful multiomic analysis. "In the next phase of growth for RADR our belief is that we can deepen our capabilities in novel ADC development and also predict combination therapy approaches using our drug candidates and existing approved immuno-oncology therapies," stated Mr. Sharma.

"Previously, the task of identifying new cancer therapies has been costly, risky, and inefficient. Specifically, studying how existing compounds and therapeutic combinations can affect different cancer subtypes often took years, whereas our platform can reduce many key aspects of this process to months. As a result, we believe our platform changes the industry paradigm in a meaningful way. We have witnessed first-hand the growing industry interest in solutions that innovate the development of precision therapeutics and combination therapies, which we believe will pave the road to new partnerships. Accordingly, we believe our growing A.I. platform will be pivotal in uncovering potential new therapeutic opportunities and developing insights into the creation of combination-therapy programs, both internally and through third-party party collaborations to drive long-term shareholder value."

RADR’s highly scalable machine-learning methods are designed to guide drug development and yield new biological insights, while also having the potential to increase response rates and improve outcomes in clinical trials. The robustness and growing number of datasets powering RADR is anticipated to continue to improve machine-learning results, accelerate automation of other features and aid oncology drug development for Lantern and its partners with an ultimate focus on benefitting cancer patients.

On November 1, 2021 Leidos (NYSE:LDOS), a FORTUNE 500 science and technology leader, reported that it was recently awarded a new task order by the Air Combat Command (ACC) Acquisition Management and Integration Center (AMIC) to support ACC intelligence, surveillance and reconnaissance (ISR) operations (Press release, Leidos, NOV 1, 2021, View Source [SID1234594652]). The single-award, firm-fixed price task order has a one-year base period of performance, four one-year options, and a total contract value of approximately $531 million if all options are exercised. Work will be performed at over 25 CONUS locations.

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"Combating global threats requires our armed forces to possess and constantly obtain critical knowledge of the strategic, operational, and tactical environments," said Leidos Defense Group President Gerry Fasano. "We look forward to leveraging our more than 33 years of strategic intelligence experience and exceptional performance on the current ACC ISR program to support our warfighters in meeting the challenges of peacetime air sovereignty and wartime air defense."

Under the contract, Leidos will provide subject matter expertise and threat mitigation support for ACC ISR operations along with a full range of intelligence support and ISR operational services that encompass analysis and assessment support, ISR training support, and intelligence support for HQ ACC Staff, subordinate NAF Staffs, Centers, and Wings.

Headquartered at Joint Base Langley-Eustis in Hampton, Virginia, the AMIC provides services acquisition solutions for ACC, the largest of the Air Force’s major commands.

On November 1, 2021 Thermo Fisher Scientific, the world leader in serving science, reported its acquisition of Belgium-based PharmaFluidics, the developer of the μPAC range of micro-chip-based chromatography columns (Press release, Lifescience Newswire, NOV 1, 2021, View Source [SID1234594649]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The µPAC portfolio of columns enhance liquid chromatography (LC) performance in biomarker, proteomics and drug research and development applications, helping biotechnology and pharmaceutical companies uncover new insights and advance scientific discovery. Through an innovative approach, separation performance and sensitivity are improved with the μPAC chromatography columns, allowing for the identification of substantially more compounds in complex biological samples. The μPAC portfolio acquisition complements Thermo Fisher’s existing chromatography solutions to deliver extended analytical capabilities to researchers.

"LC is a key analytical technique across numerous applications, and its accuracy, reproducibility and robustness is critical to the delivery of meaningful results," said Kent Davidson, vice president and general manager, high performance chromatography solutions, chromatography and mass spectrometry, Thermo Fisher Scientific. "Columns are an essential part of these workflows, and the next-generation μPAC columns push this element to a new level through innovative pillar array technology, improving the quality of data."

The μPAC columns deliver excellent separation and sensitivity to achieve greater identifications from samples with a large dynamic range, ultimately enhancing the solutions available for pharmaceutical laboratories to help meet changing needs in medical research.

On November 1, 2021, Theralink Technologies, Inc. (the "Company") reported that it entered into a Securities Purchase Agreement (the "SPA") with two investors (the "Investors") pursuant to which the Investors agreed to purchase convertible notes ("Notes") and accompanying warrants ("Warrants") for an aggregate investment amount of $1,000,000.00 (Filing, 8-K, Oncbiomune, NOV 1, 2021, View Source [SID1234594578]). The SPA contains customary representations, warranties, and covenants of the Company and Investors as detailed therein.

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The Notes have an aggregate face value of $1,000,000 and each Note bears interest at a rate of 8% per annum (which shall increase to 10% per year upon the occurrence of an "Event of Default" (as defined in the Notes)) and shall mature on November 1, 2026 (the "Maturity Date"). The Notes will be funded in two tranches on November 1, 2021 and December 1, 2021. The Notes are convertible into shares of the Company’s common stock at a conversion price equal to $0.00366 per share for any amount of principal and accrued interest remaining outstanding (subject to adjustment as provided therein). The Company may prepay the Notes at any time in an amount equal to 110% of outstanding principal balance and accrued interest.

In connection with each Note, the Investors were issued Warrants to purchase an amount of common stock equal to 20% of the shares of common stock issuable upon conversion of the Notes at an exercise price of $0.00366 per share (subject to adjustment as provided therein) until November 1, 2026. The Warrants are exercisable for cash at any time.

On November 1, 2021 Race Oncology Limited ("Race") reported it has submitted the first human ethics application to the Hunter New England Human Research Ethics Committee (NSW, Australia) seeking approval to commence an open label Phase 2 clinical trial of Zantrene (bisantrene dihydrochloride) in patients with extramedullary Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndromes (MDS) (Press release, Race Oncology, NOV 1, 2021, View Source [SID1234594187]).

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This trial (named BISECT) will be led by Associate Professor Anoop Enjeti, Director of Haematology at the Calvary Mater Newcastle and John Hunter Hospitals and is designed to use 10 high volume MDS/AML referral sites with all sites expected to be active by Q3 CY 2022. Dr Enjeti is a highly experienced clinical haematologist, having designed and led more than 25 clinical trials and is the co-chair of the MDS/AML working party for the Australasian Lymphoma and Leukaemia Group (ALLG) for Cooperative Clinical Trials.

This open label Phase 2 trial will recruit up to 60 patients with extramedullary AML or MDS using a two-stratum (arm) design. The first stratum will utilise high dose Zantrene over 7 days followed by one or more cycles of consolidation treatment of Zantrene in combination with cytarabine arabinoside (Ara-C).

The second stratum builds on work from the Chen Laboratory, City of Hope, which identified that Zantrene is able to synergize with decitabine to provide increased efficacy in mouse models of AML1,2. This stratum will use low dose Zantrene targeting FTO in combination with the oral hypomethylating agent, ASTX727 (decitabine and cedazuridine) for patients unable to tolerate high intensity chemotherapy. This stratum has been expanded to include both extramedullary AML and MDS patients.

"I am delighted to be involved with this important and novel study for patients with extramedullary AML and MDS which – due to improvements in diagnostic imaging – has been recognised to occur in up to 22% of AML patients. There is currently no agreed standard treatment for this patient population and this is one of the first therapeutic trials to focus on this important disease area. This study will improve our knowledge of extramedullary AML and hopefully result in a new treatment approach."

A/Prof Anoop Enjeti
Extramedullary AML
Extramedullary AML occurs when leukaemia spreads from the bone marrow and forms solid tumours in tissues such as the skin, breast, kidney, brain, or other organs. A 2020 prospective positron imaging trial identified that up to 22% of AML patients have the extramedullary form3. Extramedullary AML patients have no clinically approved treatments and limited experimental treatment options, with many clinical trials explicitly excluding this difficult to treat form of AML.

A Phase 2 clinical trial of Zantrene in relapsed or refractory (r/r) AML patients by a team led by Professor Arnon Nagler of the Chaim Sheba Medical Center, Israel reported a 100% clinical response rate (4/4 patients) in those patients with the extramedullary form of this deadly cancer (ASX announcement: 16 June 2020).

"We are excited to commence this important study that explores treatment for a poorly served population of AML and MDS patients. This is a novel study design and the use of Zantrene in both high and low dose levels is unique. The high dose stratum extends our legacy AML credentials, while the low dose represents the start of our FTO targeted clinical program."

Race CMO Dr David Fuller

Myelodysplastic Syndromes (MDS)
MDS are a group of blood cancers which affect the production of normal blood cells in the bone marrow. These include chronic myelomonocytic leukaemia (CMML), juvenile myelomonocytic leukaemia (JMML), atypical chronic myeloid leukaemia (aCML) and myelodysplastic/ myeloproliferative neoplasms unclassifiable (MDS/MPN)4.

MDS has a very high risk (1 in 3) of the patient progressing to AML. There are more than 10,000 patients diagnosed with MDS each year in the USA which is approximately half the rate of AML.

"This study supports our Pillar 3 registration ambition to see Zantrene’s historical safety and efficacy in AML demonstrated with superior drug combinations that may benefit patients who remain challenged by initial treatment failures. It is pleasing to be able to open up this trial to MDS patients who are equally in need of new improved treatment options."

Race CEO & MD Phillip Lynch
Clinical Trial Design
This open label Phase 2 trial will recruit up to 60 patients with 18F-FDG PET/CT imaging-identified extramedullary AML at 10 clinical sites using a two-stratum (arm) design. The first stratum will utilise Zantrene as a high dose, single agent, treatment over 7 days in patients with extramedullary AML who are able to tolerate high intensity chemotherapy, followed by one or more cycles of consolidation treatment of Zantrene in combination with Ara-C, a standard of care drug.

The second stratum will use Zantrene as a low dose FTO-targeted agent in combination with the oral hypomethylating agent, ASTX727 for MDS/AML patients unable to tolerate high intensity chemotherapy. Published preclinical data from the City of Hope Hospital by Professor Chen’s Laboratory identified that Zantrene is able to synergize with decitabine2. In mouse models of AML the combination provided improved therapeutic efficacy with, lower toxicity compared to when either drug was used alone3.

The primary endpoint will be complete response (CR) and complete response with incomplete haematological recovery (CRi) with an aim of bridging to an allogeneic hematopoietic stem cell transplant (Stratum 1), or safety and tolerability (Stratum 2). Key secondary endpoints include safety and tolerability of Zantrene, overall and event-free survival, and FTO expression or other biomarkers with response to treatment.

Clinical Trial Summary
Study Title An open label Phase 2 study of high dose bisantrene with cytarabine arabinoside (Ara-C) or low dose bisantrene with oral decitabine for treatment of Acute Myeloid Leukemia patients with extramedullary disease (BISECT)
Phase of Development Phase 2
Active Ingredient Zantrene (bisantrene dihydrochloride)
Study Description A two-stratum trial of Zantrene in patients with extramedullary AML or MDS diagnosed by 18F-FDG PET/CT imaging.
Principle Investigator A/Prof Anoop Enjeti
Sponsor Race Oncology
Indication/population Adult men and women ≥18 years of age with AML or MDS presenting with non-CNS extramedullary disease.
Number of Subjects Stratum 1: up to 30 patients Stratum 2: 4 -10 patients (dose escalation stage); up to 30 patients in the expansion stage
Study Period 36 – 40 months
Study Design A two strata Phase 2, open-label study of high dose bisantrene treatment given as a monotherapy induction and in combination with Ara-C as consolidation (Stratum 1) and lower dose bisantrene in combination with oral decitabine (ASTX727) (Stratum 2) in patients with extramedullary AML or MDS. As the patient population is considered without existing treatment options, a comparator arm will not be used.
Statistical methods Bayesian Optimal Interval (BOIN) model-based design based on observed response rate of 30% for RR AML where the true response rate is expected to be <20% applying a 90% power.
End Points Primary (Stratum 1): Achievement of a complete response (CR) or complete response with incomplete count recovery (CRi). Primary (Stratum 2): Tolerability and safety. Key Secondary: Achievement of a PET/radiologic overall response, i.e. complete or partial metabolic response, after cycles 1, 2 and 4. Other Secondary: FTO and other biomarker status, event free survival, overall survival
Participating Centres 10 sites
Indicative Timelines
The trial is expected to take 36 to 40 months to complete with full patient recruitment over approximately 18 months.

Q&A
What is ASTX727 and why was it chosen for the trial?
ASTXZ727 (trademark INQOVI) is a oral formulation of decitabine, a nucleoside metabolic inhibitor, and cedazuridine, a cytidine deaminase inhibitor and has been approved by the FDA for treatment of adult patients with MDS. It is currently in late stage clinical trials for AML patients.

Astex Pharmaceuticals /Otsuka Pharmaceuticals intends to provide ASTX727 free of charge for this trial.

Will this trial support orphan drug registration of Zantrene under the FDA 505(b)(2) pathway?
Yes. The Stratum 1 patients will be treated as per the historical Zantrene AML trials (i.e. 250 mg/m2/day over 7 days). This trial will build the modern and historical data.

Stratum 2 may provide clinical evidence for the use of Zantrene in patients too old or ill to be able to tolerate high intensity chemotherapy.

Does this trial target FTO in AML & MDS patients?
Yes. This trial builds on the preclinical studies of our advisor Professor Jianjun Chen of the City of Hope Hospital. His team discovered in AML cells that inhibition of FTO with Zantrene (CS1) synergises with the hypomethylating standard of care drug, decitabine. This combination will be clinically explored in patients unable to tolerate high intensity chemotherapy (Stratum 2).

Why was the trial split into two stratums?
There is currently no standard of care treatment for the extramedullary form of AML or MDS. As more than 50% of AML patients are not healthy enough to tolerate high intensity chemotherapy, we wanted to ensure we could offer a treatment option for all patients enrolled in the trial. In addition, success with the low intensity FTO-targeted regime could potentially be an attractive alternative for healthier patients unwilling to undertake intense chemotherapy.

Will you need to do a separate Phase 3 trial in the US to enable FDA registration?
No. By utilising the FDA 505(b)(2) approval pathway our clinical advisors have indicated that FDA approval can be obtained using a limited number of Phase 2 trials. Race intents to run three limited Phase 2 trials in Australia, USA and the EU and seek Fast Track FDA designation and EMA label approval for this orphan indication with high unmet medical need.

When can shareholders expect progress updates on the trial?
This trial is open label in nature, so patient outcome results are obtained as patients are treated. We intend to announce progress updates on a regular basis, but not at the individual patient level. The first patient is expected to begin treatment soon after human ethical approval is obtained.

References
1. Prof Chen recently joined Race’s Scientific Advisory Board (ASX Announcements: 16 April 2021).

2. Su, R., Dong, L., Li, Y., Gao, M., Han, L., Wunderlich, M., et al. (2020). Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion. Cancer Cell, 38(1), 79–96.e11.

3. Stölzel, F., Lüer, T., Löck, S., Parmentier, S., Kuithan, F., Kramer, M., et al. (2020). The prevalence of extramedullary acute myeloid leukemia detected by 18FDG-PET/CT: final results from the prospective PETAML trial. Haematologica, 105(6), 1552–1558.

4. www.leukaemia.org.au/blood-cancer-information/types-of-blood-cancer/myelodysplastic-syndromes/