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Lantern Pharma Oncology Drug Portfolio

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Taking a novel approach to drug development

Pipeline

Lantern’s current portfolio consists of four drug candidates and an ADC program across 8 tumor targets, including two phase 2 programs. Lantern believes that the use of machine learning, genomics and computational methods can help accelerate the development and commercialization of small molecule-based therapies. These drugs can be targeted to patients whose genomic profile identifies them as having the highest probability of benefiting from the drug, thereby creating the potential to achieve better outcomes.

Lantern Pharma Oncology Pipeline

Drug Name
Indication
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-100

mCRPC
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-300

NSCLC
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-184

GBM
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Pediatric ATRT
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Pancreatic
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Bladder
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Prostate
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-284

Hematologic & Solid Tumors
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-A18 (ADC Programs)

Solid Tumor
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration
Drug Name
Indication
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-100

mCRPC
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-300

NSCLC
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Pancreatic
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-184

CNS Cancers - Glioblastoma
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-184

CNS Cancers - ATRT
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Bladder
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-184

Prostate
Discovery
Preclinical
IND/CTA Filed
Phase I
Phase II
Phase III
Pre-Registration

LP-284

Hematologic Cancers
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

LP-A18

ADC - Solid Tumors
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration

Lantern Pharma Oncology Portfolio

LP-284

Mechanism of Action

LP-284, is a stereoisomer of LP-184 and a new chemical entity currently in early preclinical R&D stages. It is a distinct pharmaceutical agent with cancer cell-killing activity differing from LP-184 in terms of target indications, potency, metabolism, pharmacokinetics and toxicity. Its mechanism of action is likely related to DNA-damage and DNA-repair inhibition in cancer cells.

Background

LP-284 is a fully synthetic molecule belonging to the new generation of acylfulvenes, a family of naturally-derived anti-cancer drug candidates. It is currently being evaluated for activity in a spectrum of hematological cancers. Together with the work of collaborators, the roadmap to advancement of LP-284 to the clinic includes identification and validation of target indications, response gene signature development leading to IND-enabling pharmacokinetic profiling, tolerability and dose range finding studies followed by clinical protocol development.

LP-184
LP-184 Chemical Structure

Mechanism of Action

LP-184, or hydroxyureamethylacylfulvene, is a small molecule drug candidate currently in preclinical development. It is a next generation alkylating agent that preferentially damages DNA in cancer cells that overexpress certain biomarkers and is from the fulvene class of compounds.

Background

LP-184 is a promising member of a new generation of acylfulvenes, a family of naturally-derived anti-cancer drug candidates. In preclinical studies, LP-184 has shown significantly enhanced anti-tumor activity and substantially reduced toxicity as compared to earlier generation acylfulvenes. In addition, we have used our RADR™ platform together with the work of collaborators, to develop a patient-specific biomarker test predictive of LP-184’s efficacy. We plan on using this test to facilitate patient selection in our planned Phase 1 clinical trial for LP-184.

LP-300
LP-300 Chemical Structure

Mechanism of Action

LP-300, or Disodium 2,2’-dithio-bis-ethane sulfonate, is a small molecule entity with cysteine modifying activity on select proteins. LP-300 works to modulate multiple cellular pathways simultaneously and is a potential first-in-class combination agent indicated in NSCLC.LP-300 shows cysteine modifying activity on select proteins (ALK), and has shown that it modulates protein function (EGFR, MET, and ROS1). It also acts as a chemo-sensitizer for combination therapies by inactivating proteins that are modulating cellular redox status and drug resistance (TRX, GRX) and possesses chemoprotectant activity that reduces toxicities associated with Taxane / Platinum based chemotherapies.

Background

LP-300, originally branded as Tavocept®, is a molecular entity that we believe may be capable of ameliorating the toxic side effects of chemotherapeutic drugs such as cisplatin. It also acts as a chemoenhancer and has been studied in multiple randomized, controlled, multi-center non-small cell lung cancer (NSCLC) trials that included administration of either paclitaxel and cisplatin and/or docetaxel and cisplatin. Retrospective analyses of the results of a multi-country phase III lung cancer trial in subgroups of adenocarcinoma patients receiving LP-300, paclitaxel and cisplatin demonstrated substantial improvement in overall survival, particularly among female non-smokers, where a 13.6 month improvement in overall survival (p-value 0.0167, Hazard Ration 0.367) in favor of LP-300 was observed, as compared to placebo in the subgroup of paclitaxel/cisplatin-treated patients. We are focused on repositioning LP-300 as a potential combination therapy for non-smoking (or never-smoking) female NSCLC patients with histologically defined adenocarcinoma. Currently there is no approved therapy specifically for the growing indication of non-smokers (or never-smoking) with NSCLC, and female non-smokers appear to be uniquely responsive to LP-300. With both chemoprotective and chemosensitizing activity, LP-300 has potential as a combination agent or adjuvant in front line, second line or salvage therapy in newly diagnosed, relapsed, metastatic or advanced NSCLC for overall survival enhancement and toxicity alleviation from primary chemotherapy or standard of care.

LP-100

Mechanism of Action

LP-100 or 6-hydroxymethylacylfulvene exploits cancer cells’ deficiency in DNA repair mechanisms. LP-100 shows multiple cytotoxic effects on tumor cell biology such as DNA adduct formation, RNA polymerase stalling and redox protein modification. It demonstrates enhanced sensitivity in DNA repair deficient (e.g. ERCC3 mutant or knockout) in vitro and in vivo models. LP-100 leads to rapid inhibition of DNA synthesis and induction of DNA damage. LP-100 is a monofunctional covalent DNA binder that inhibits DNA synthesis and replication, affects cell cycle and induces apoptosis. DNA repair of LP-100-induced lesions is mediated by components of the transcription-coupled nucleotide excision repair (TC-NER) pathway. LP-100 produces damage to DNA that can only be repaired by the TC-NER pathway.

Background

LP-100 was first developed by MGI Pharma and later in collaboration with global pharma company, Eisai.  LP-100 has shown strong clinical anti-tumor activity against a 10-12% of patients with multidrug resistant advanced prostate cancer with notable resolution of bone metastases.  Lantern’s process was to uncover a genomic signature that determines potential responders, develop suitable preclinical data, and successfully out-license it to Oncology Venture (a European Biotech) in 18 months. LP-100 is currently in an active phase II clinical trial in in AR-targeted and Docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC) patients.

LP-100

Indication
Collaborator
mCRPC {Metastatic Hormone Refractory (Castration Resistant, Androgen-Independent) Prostate Cancer}
Collaborator
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Mechanism of Action and Background
LP-100 Chemical Structure

Mechanism of Action

LP-100 or 6-hydroxymethylacylfulvene exploits cancer cells’ deficiency in DNA repair mechanisms. LP-100 shows multiple cytotoxic effects on tumor cell biology such as DNA adduct formation, RNA polymerase stalling and redox protein modification. It demonstrates enhanced sensitivity in DNA repair deficient (e.g. ERCC3 mutant or knockout) in vitro and in vivo models. LP-100 leads to rapid inhibition of DNA synthesis and induction of DNA damage. LP-100 is a monofunctional covalent DNA binder that inhibits DNA synthesis and replication, affects cell cycle and induces apoptosis. DNA repair of LP-100-induced lesions is mediated by components of the transcription-coupled nucleotide excision repair (TC-NER) pathway. LP-100 produces damage to DNA that can be preferentially repaired by the TC-NER pathway.

Background

LP-100 has the potential to be an important compound — either as monotherapy or in combination — for several challenging cancers that are impacting patients globally. LP-100 is in an existing genomic-signature guided phase 2 clinical trial in Denmark for patients with metastatic castration resistant prostate cancer (mCRPC). 9 patients (out of a targeted enrollment of 27) have been treated in the trial. The median overall survival (OS) for the initial group of 9 patients has been approximately 12.5 months, which is an improvement over other similar fourth-line treatment regimens for mCRPC.

Recent opportunities have also been identified for the potential use of LP-100 in cancers with DNA repair deficiencies, including potential to treat bladder and prostate cancer patients who have a mutation in the ERCC2/3 genes.

There were over 42,900 cases of metastatic castration-resistant prostate cancer in the US during 2020, and over 170,000 cases globally. Approximately 25-30% of these patients in the US and globally, need treatment options in the third-line setting, or later. In addition, approximately 25-30% of all metastatic prostate cancers have been observed to have mutations in DNA repair genes.

LP-300

Indication
Collaborator
NSCLC (Non-Small Cell Lung Cancer)
Collaborator
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Mechanism of Action and Background
LP-300 Chemical Structure

Mechanism of Action

LP-300, or Disodium 2,2’-dithio-bis-ethane sulfonate, is a small molecule entity with cysteine modifying activity on select proteins. LP-300 works to modulate multiple cellular pathways simultaneously and is a potential first-in-class combination agent indicated in NSCLC. LP-300 shows cysteine modifying activity on select proteins (ALK), and has shown that it modulates protein function (EGFR, MET, and ROS1). It also acts as a chemo-sensitizer for combination therapies by inactivating proteins that are modulating cellular redox status and drug resistance (TRX, GRX) and possesses chemoprotectant activity that reduces toxicities associated with Taxane / Platinum based chemotherapies.

Background

LP-300, originally branded as Tavocept®, is a late stage investigational new drug that has been studied in multiple randomized, controlled, multi-center non-small cell lung cancer (NSCLC) trials. It has been shown to have chemo-enhancing and nephroprotective effects. The last clinical trial conducted was an international Phase III study in which patients with advanced lung adenocarcinoma received LP-300 in combination with cisplatin and paclitaxel or docetaxel (test arm) or cisplatin and paclitaxel or docetaxel (standard of care/control arm). Although the study did not meet endpoints in the overall patient population, retrospective analyses demonstrated that the addition of LP-300 significantly increased overall survival in the specific subset of never-smoker patients. The overall median survival in never-smokers was 13.2 months for those who received standard of care only compared to 25.2 months (n= 87; p-value= 0.046) for those who received standard of care plus LP-300, representing an increase of 91%. We are now repositioning LP-300 as a potential combination therapy for never-smoking NSCLC patients with histologically defined adenocarcinoma. Currently there is no approved therapy specifically for the growing indication of never-smokers (or non-smokers) with NSCLC. With both chemoprotective and chemosensitizing activity, LP-300 has potential to increase overall survival and alleviate toxicities from primary chemotherapy in front line, second line or salvage therapy in newly diagnosed, relapsed, metastatic or advanced NSCLC.

LP-184

Indication
Collaborator
Pancreatic
Collaborator
Fox Chase Cancer Center & Champions Oncology
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Indication
Collaborator
CNS Cancers - Glioblastoma
Collaborator
John Hopkins School of Medicine
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Indication
Collaborator
CNS Cancers - ATRT
Collaborator
John Hopkins School of Medicine
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Indication
Collaborator
Bladder
Collaborator
Fox Chase Cancer Center
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Indication
Collaborator
Prostate Cancer
Collaborator
Georgetown University
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Mechanism of Action and Background
LP-184 Chemical Structure

Mechanism of Action

LP-184 is a prodrug converted into an active alkylating agent by threshold expression level of the oxidoreductase enzyme prostaglandin reductase 1 (PTGR1), which is often elevated in multiple tumor types. The conversion of LP-184 specifically within the tumor is less likely to cause toxicities to normal tissues.

Background

LP-184 (hydroxyureamethylacylfulvene) is a small molecule drug candidate and “next generation” alkylating agent with an ability to cross the blood-brain barrier. It is highly potent and synthetically lethal in cancers harboring defects in multiple DNA damage repair and recombination pathways (HR/NER).

LP-184 demonstrated remarkable efficacy against a range of cell lines, in vivo and ex vivo models validated by in-silico predictions generated by our RADR® A.I. platform. Based upon highly encouraging preclinical data, the U.S. Food and Drug Administration (FDA) granted LP-184 Orphan Drug Designation for the treatment of pancreatic cancer and glioblastoma multiforme and other malignant gliomas in August 2021.

LP-184 will be developed for many targeted oncology indications. Lantern Pharma looks forward to further advancing LP-184 as a new, potent treatment option in genetically-defined subsets of patient populations in areas of high unmet clinical need in pancreatic cancers and GBM (including MGMT-unmethylated GBMs, temozolomide-resistant GBMs, and EGFR-aberrant or recurrent GBMs.)

LP-184 is selectively activated by the enzyme prostaglandin reductase 1 (PTGR1).

LP-284

Indication
Collaborator
Hematologic Cancers
Collaborator
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
Mechanism of Action and Background
LP-284 Chemical Structure

Mechanism of Action

  • LP-284 is the stereoisomer (enantiomer) of LP-184. This small molecule drug candidate is a new chemical entity which is in early stages of preclinical research and development. The enantiomers possess distinct cancer cell-killing activity, and these differences can be better understood through the use of data-driven methodologies. Lantern expects to apply these insights to develop LP-284 in cancer indications that are different and complementary to those being targeted by LP-184.
  • LP-284 can potentially act by targeting defective DNA damage repair pathways of cancer cells.

Background

LP-284 is a fully synthetic molecule belonging to the new generation of acylfulvenes, a family of naturally derived anti-cancer drug candidates. While LP-184 shows potency in solid cancer, LP-284 was primarily developed as an analogue which shows selective efficacy against hematologic cancer. LP-284 is currently being evaluated for activity in a wide spectrum of hematological cancers.

Together with the work of collaborators, the roadmap to advancement of LP-284 to the clinic includes identification and validation of target indications, response gene signature development leading to IND-enabling pharmacokinetic profiling, and tolerability and dose range finding studies followed by clinical protocol development.

LP-A18

Indication
Collaborator
ADC - Solid Tumors
Collaborator
Discovery
Preclinical
IND Enabling
Phase I
Phase II
Phase III
Pre-Registration
"We are in the golden age of A.I. where we are able to significantly impact the speed and precision at which we develop new drugs."
Panna Sharma
PRESIDENT & CEO, LANTERN PHARMA