LTRN: Lantern Calls On Califia for Antibody Drug Conjugates

By John Vandermosten, CFA

NASDAQ:LTRN

On January 4, 2021, Lantern Pharma LTRN announced the launch of an antibody-drug conjugate (ADC) program through a partnership with San Diego-based Califia Pharma. Lantern has matched several approved antibodies with in its portfolio compatible with existing antibodies and linkers using its RADR (1) AI algorithm. Encouraged by Gilead's $21 billion acquisition of ADC leader Immunomedics (2), Lantern forged a relationship with Califia to link its existing candidates with proven antibodies to address cancers where drug resistance has created an unmet need.

Using Califia's linkers, Lantern conducted lab work that demonstrated improved efficacy at lower doses when LP-184 was combined with existing cancer antibodies. The lower levels of drug also resulted in decreased toxicity. Califia's patented linkers, payloads and conjugations provide a construct to combine approved immuno-oncology antibodies with Lantern's alkylating and DNA damaging agents. ADC development will target both solid tumors and blood cancers where drug resistance and systemic toxicity are key issues. Lantern's LP-100 is also being considered for the approach.

Antibody Drug Conjugates

Antibodies

Antibodies are proteins produced by B-lymphocytes in response to foreign antigens, most commonly bacteria and viruses as a part of the immune response. These biologics are often thought of as flags to mark pathogens for sequestering and destruction with the shape of the antibody binding site determining its specificity. Antibodies are engineered to target specific antigens, which include proteins, sugars or even nucleic acids. In addition to foreign immunogenic agents such as bacteria and viruses, antibodies can identify and bind to antigens, receptors or epitopes specific to cancer cells, allowing for targeted identification of malignant cells.

Exhibit I – Antibody Drug Conjugate (3)

Linkers

When the antibody is linked to a payload, which can be either a cytotoxic agent or a drug, it is termed an antibody drug conjugate (ADC). The ADC is able to bind to the cell, providing accurate delivery of the conjugate to the desired cell. Frequently, the ADC is endocytosed where the link is cleaved and the payload released. Linkers attach to amino acids on the antibody, frequently via thiol chemistry of surface cysteines or lysines. Linkers are critical to the success of the ADC and their type determines when the cytotoxic payload will be released.

Califia Pharma

Califia Pharma offers a portfolio of linker strategies that complement Lantern's LP-100 and LP-184 allowing for lower concentrations and increased specificity. The antibodies that Lantern is considering in conjunction with its candidates are as yet unidentified but will soon be off patent, providing well understood, battle-tested and potentially less-expensive biologics as part of the combination therapy for cancer indications.

Choice of linkers depends upon both the antibody and payload. Califia has identified and documented many linkers amenable to conjugate LP-100 or LP-184. In fact, the original researcher for LP-184 is Michael Kelner, M.D., professor at the University of California San Diego Medical Center, who is also the CEO of Califia (4). The choice of linkers is important for compatibility and internalizing the payload inside the cell.

Lantern Portfolio

Lantern has three candidates in its portfolio. The most advanced is LP-100, or Irofulven, which is being developed by partner Allarity Therapeutics for an indication in prostate cancer. It is in a Phase II trial and expected to read out in 1H:21. Lead internal candidate LP-300 will begin a Phase II trial seeking an indication in never smoker non-small cell lung cancer (NSCLC). We anticipate the trial will begin in the next few months. The third candidate, LP-184, is in the preclinical stage. The agent will be developed for indications in solid tumors with a defined genomic signature such as ovarian, breast, liver, kidney and thyroid cancers and in glioblastoma. Lantern will evaluate LP-100 and LP-184 as independent candidates and as part of its newly announced ADC program. Safety has been established and responsive subpopulations identified.

Exhibit II – Lantern Portfolio (5)

RADR

Response Algorithm for Drug Positioning and Rescue or RADR is Lantern's proprietary algorithm and platform that seeks to predict therapeutic response based on personal and physiological features. The platform allows Lantern to salvage clinically-failed drugs by selecting for responsive patients and running new clinical trials on responsive subpopulations. The platform can estimate drug sensitivity, classify a patient as a responder or non-responder and identify predictive biomarkers for each drug-tumor combination.

Exhibit III – RADR Workflow (6)

RADR's predictive algorithm is based on an artificial neural network. It can also predict using support vector machine, random forest, k-nearest-neighbors, logistic regression and penalized multivariate regression models. Each algorithm is evaluated using accuracy, receiver operating characteristic (ROC) curve area, sensitivity, specificity, precision, root mean square error (RMSE), and mean absolute error. The RADR feature reduction algorithm further reduces the almost 500 predictive genes to 10-30 that best predict both drug sensitivity and can classify responders and non-responders. For detail on Lantern's RADR platform and its programs, please see our initiation.

Summary

Lantern has taken the initiative to leverage ADCs in combination with two of its clinical-stage chemotherapies. The firm has enlisted Califia to help it use its portfolio candidates to develop ADCs in new cancer indications. Lantern will simultaneously advance its LP-300 program in non-smoker NSCLC and its ADC program.

Key reasons to own Lantern Pharma Inc. shares:

‣ Proprietary RADR AI-driven algorithm for detecting genetic/biomarker signatures

‣ Opportunities to salvage failed drugs, for which safety has already been clinically validated

‣ AI-guided drug development can reduce costs and accelerate advancement of portfolio candidates.

• Build from existing preclinical and clinical work

• Pursue orphan indications and personalized medicine

• Generate pivotal data with less expensive, targeted trials

• Use modeling and complex algorithms to reduce failure risk

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1. Lantern's proprietary AI platform is entitled Response Algorithm for Drug Positioning and Rescue (RADR).

2. Immunomedics developed next-generation ADC technology and obtained FDA approval for Trodelvy in metastatic triple negative breast cancer in April 2020.

3. Polakis, Paul. Antibody Drug Conjugates for Cancer Therapy. Pharmacological Reviews, January 2016.

4. https://ucsdnews.ucsd.edu/archive/newsrel/science/mdmushrm.htm

5. Source: Lantern Corporate Presentation, August 2020.

6. Lantern Pharma Precision Oncology Whitepaper