Programs-From Half-Life to Full-Life.

Prostate-specific membrane antigen, PSMA

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein. High levels of PSMA expression are found on the membranes of aggressive types of tumor endothelial cells, prostate cancer, and other human cancers. 68Ga-PSMA-11, which significantly improves the detection of cancer cells, is the first FDA-approved agent for the imaging of PSMA-positive lesions via positron emission tomography (PET). Thus, this compound provides a more effective selection strategy for the identification of prostate cancer patients who may benefit from PSMA-targeted therapy. The recent FDA approval of 177Lu-PSMA-617 has indeed demonstrated promising results from PSMA-targeted radiopharmaceutical therapy (RPT) targeting patients with metastatic castration-resistant prostate cancer (mCRPC). The use of first generation PSMA targeted RPT has been limited in advanced prostate cancer due to concerns related to potential radiation toxicity. Thus, PSMA appears to be a good theranostic target meriting further research and development.

1.S Boinapally. et al. (2021) Sci Rep. 11:7114

2.U Hennrich. et al. (2021) Pharmaceuticals (Basel). 14:713

3.DP Petrylak. et al. (2019) Prostate. 76:604

Somatostatin Receptor 2 (SSTR2)

Somatostatin type 2 receptor (SSTR2) belongs to the G-protein coupled receptor (GPCR) family that is aberrantly regulated in various tumors. It has been well established that SSTR2 is highly and broadly overexpressed in certain neuroendocrine tumors (NETs). Synthetic molecules that mimic the native SSTR2 ligand, somatostatin, have been successfully developed and approved as a theranostic-therapeutic pair, Netspot® (68Ga-DOTATATE) and Lutathera® (177Lu-DOTATATE), for detecting and treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the objective radiographic response rate (ORR) for Lutathera® is 18% with nearly no treatment options after Lutathera®, and GEP-NETs only represents half of total NET incidents. Separately, SSTR2 is also overexpressed in small cell lung cancer (SCLC) and other tumor types, and SSTR2-targeted radiotherapy has shown certain efficacy for their treatment but still at very early development stages. Collectively, there is still sizable opportunities of SSTR2-targeted radiotherapies and associated significant unmet medical needs. With an Ac-225-based alpha-therapy that is targeted via our novel SSTR2 vector, we aim to expand the indication of SSTR2-targeted radiotherapies from GEP-NETs to other NET subtypes, SCLC and other SSTR2-postive indications whose tumors are SSTR2-medium/low expressed or resistant/refractory to Lutathera®.

Neurotensin receptor type 1, NTSR1

Neurotensin receptor type 1, NTSR1 (also called NTR-1) binds to neurotensin (NT), a 13-amino-acid peptide (or tridecapeptide) mainly secreted from the central nervous system and gastrointestinal tract. NTSR1 comprises 424 amino acids and belongs to a large superfamily (Class A) of 7-transmembrane (G protein-coupled) receptors. NTSR1 has high affinity towards NT. Signaling of the NT/ NTSR1 complex mediates multiple biological processes by G proteins that subsequently activate a phosphoinositide (PI)-derived second messenger system. Downstream signaling leads to the activation of Protein kinase C (PKC) and the enhancement of intracellular calcium mobilization, resulting in cell proliferation, survival, migration, and invasion. Importantly, higher expression of NT and NTSR1 were found in human cancers including pancreatic, lung, breast, prostate, and colon, among others. In vivo evidence suggests that NT/ NTSR1 signaling correlates with tumor growth.

1.S Nikolaou. et al. (2020) Cell Commun Signal. 18:68

2.Zherui Wu. et al. (2013) Front Endocrinol (Lausanne). 3: 184

3.N Christou. et al. (2020) Cell Death Dis. 11: 1027

Mesenchymal-epithelial transition factor, c-MET

Mesenchymal-epithelial transition factor (c-MET), a member of the receptor tyrosine kinase family, highly expressed in nearly all malignant tumors making it an attractive target for RDC therapy. However, despite the clinical validation of c-MET by various modalities including ADC, the indication has been limited to non-small cell lung cancer (NSCLC). RDC therapy holds the promise of significantly expanding the current c-MET treatment landscape. FL-261 is a first-in-class radioligand therapy targeting c-MET which demonstrates potent and selective binding to c-MET protein, high and specific tumor uptake and promising anti-tumor activities in multiple xenograft models with different levels of c-MET expression.

B7 Homolog 3, B7H3

B7H3, also known as CD276, is a type I transmembrane protein and a member of the B7 family. B7H3 is highly expressed across various solid tumors including lung, esophageal, prostate, and breast cancers. Antibody drug conjugate (ADC) therapies targeting B7H3 have demonstrated promising antitumor activities in clinical studies. Radionuclide drug conjugates (RDCs) hold the promise of delivering superior efficacy and overcoming the tumor resistance to B7H3-ADC therapies. FL-802 is a first-in-class radioligand therapy targeting B7H3 which exhibits potent B7H3 binding affinity in the in vitro assays, and high and specific tumor uptake and promising tumor growth suppression efficacy in multiple xenograft mouse models.

United States (US) Expanded Access Policy

The 21st Century Cares Act, enacted as US law in 2016, requires manufacturers of investigational drugs intended to treat serious diseases or conditions to make publicly available their policy for providing expanded access to such products. Expanded access, also referred to as compassionate use, is a mechanism for enabling the use of an investigational therapy outside of a clinical trial when the primary purpose is to diagnose, prevent or treat a serious condition in patients. This is in contrast to clinical trials, where more comprehensive safety and efficacy data are generally collected.

While Full-Life fully understand the importance of Expanded Access Programs (EAPs) in certain circumstances, our perspective at this time is that participation in our clinical studies is the most appropriate way for patients in the US to gain access to this investigational therapy.

Accordingly, it is currently not available via an EAP in the US.

We encourage patients to speak with their health care team about the possibility of participation in a clinical trial.

Additional information regarding the ongoing trials can be found at clinicaltrials.gov (ID number NCT06492122), or by emailing expanded.access@t-full.com.

As more clinical data on the safety and efficacy become available, Full-Life will review and may update its policy on expanded access. This web page will be updated accordingly, and appropriate information on how to apply for expanded access will be provided.