AREA: COVID-19
PRODUCT: AntiCovir (AP-003)
INDICATION: Early stage COVID-19
STATUS: Randomized, double-blind, placebo controlled trial, powered for Phase 3 registration

DISCOVERY PRE-CLINICAL

IND

Phase 1

Phase 2

Phase 3

AREA: HPV GENITAL (Female)
PRODUCT: AP-001
INDICATION: HPV Cervical High grade intraepithelial lesion (HSIL)
STATUS: Randomized, double-blind Phase 2b to start Q1 2021

DISCOVERY PRE-CLINICAL

IND

Phase 1

Phase 2

Phase 3

AREA: Solid Tumors with Bone Metastases or at Risk of Bone Metastases
PRODUCT: AP-002
INDICATION: Solid tumors (with focus on breast, lung and prostate cancers)
STATUS: Phase 1-2 [NCT04143789]; Ongoing

DISCOVERY PRE-CLINICAL

IND

Phase 1

Phase 2

Phase 3

AP-003

BLife Therapeutics is planning clinical trials of AP-003 to test the efficacy of IFNa2b for treatment of COVID-19. AP-003 is being developed as a novel interferon alpha2b (IFNa2b) inhalation formulation.

IFNa2b has been used to treat COVID 19 in China.² Subject to receiving marketing authorization, AP-003 could potentially be used to treat patients early after COVID 19 infection which may potentially prevent the progression to severe disease and need for hospitalization.³

  1. Subject to successful outcome of clinical trials and obtaining market authorization
  2. Dong et al, 2020; Lu, 2020; Shen & Yang, 2020; Zhou et al, 2020
  3. Altum Clin Protocol ALT 003 COV 01 2020 04 30

If successful in clinical trials, AP-003 may potentially be positioned as an initial treatment for COVID 19 and similar viruses.

For more information please see the full investor presentation.

WHY AP-003

SARS CoV 2 coronavirus causes COVID 19. SARS CoV viruses block interferon production in infected cells, allowing the virus to continue replicating unabated ¹.

Treatment with interferon may overcome that block, potentially restoring cells normal anti viral activity.

Interferon alpha 2b (IFNa2b) is a potential treatment for COVID 19 ².

IFNa2b (inhaled) has been used in China on COVID 19 patients.

AP-003 may be given by inhalation at the first signs of COVID 19 with following projected outcomes according to Altum Clin Protocol ALT 003 COV 01 2020 05 04 rationale:

  • AP-003 inhalation applies INFa2b directly to the lungs which may enable infected cells to halt viral replication.
  • AP-003 inhalation may help to restore the initial immune response to COVID 19.
  • AP-003 inhalation 1st proposed target indication: people at higher risk to develop severe COVID 19 disease
  • Potential Result: Reduction of the overall hospitalization rate, long term tissue damage and death by reducing the severity of the disease
  • Potential prevention of long term damage to the lung, heart, kidney and the brain

AP-002

Novel Anti-Tumor Agent; Dual-acting:
Anti-tumor + Anti-bone Breakdown

AP-002 is a novel, orally bioavailable gallium based small molecule NCE. In contrast to currently available bone modifying agents, AP-002 uniquely has both anti-bone resorption and direct anti-tumor cell killing activity. This positions it ideally to treat cancer metastatic to the bone. Bone metastases often result in severe pain, spinal cord compression and cancer-induced bone fractures, collectively referred to as skeletal related events (SREs). A life threatening consequence of cancer induced bone resorption is hypercalcemia of malignancy.

The present treatments for cancer-induced bone resorption conditions are either bisphosphonates (e.g. zoledronic acid; Zometa®) or the anti-RANKL MAb, denosumab (Xgeva®). Both have undesirable side effects, both need administration by healthcare professionals (intravenous or subcutaneous), and neither of them have direct anti-tumor activity. In a recent large (4,500 patient) placebo controlled trial in breast cancer, denosumab failed to improve survival.

The AP-002 US IND is approved and its Phase 1-2 trial in solid tumors with bone metastases or at risk of bone metastases is planned to start July 2019. Focus in the Phase 2 part of the trial will be on breast, lung and prostate cancers.


Preclinical studies show that AP-002 selectivity inhibits osteoclast differentiation and bone resorption, with a different mechanism of action from other anti-bone resorption agents. In addition, the preclinical studies have also shown that AP-002 promotes the growth of osteoblasts (the bone forming cells). Unlike other anti-bone resorption agents, AP-002 has been shown in in vitro and in vivo studies to have direct anti-tumor activity. Additionally, studies demonstrate that AP-002 is synergistic in combination with a range of other anti-tumor agents. Therefore, AP-002 is ideally positioned to be developed as an oral anti-cancer drug that inhibits bone resorption, that could be adjunctive to other anti-cancer therapies. Altum also intends to develop AP-002 in non-cancer bone resorption indications, such as severe osteoporosis.

References:

Wang et al. 2018: AP-002: A novel inhibitor of osteoclast differentiation and function without disruption of osteogenesis. American Society Bone & Mineral Research (ASBMR) Annual Conference 2018
https://am.asco.org/denosumab-does-not-improve-bone-metastasis%E2%80%93free-breast-cancer-survival
https://www.medscape.com/viewarticle/899729?nlid=124051_4503&src=wnl_dne_180725_mscpedit&uac=180258EY&impID=1694202&faf=1
https://www.loyolamedicine.org/news/osteoporosis-drug-holidays-bone-fractures

AP-001

An Effective HPV Treatment
Patient Administered

AP-001 is a topical delivery system that incorporates interferon alpha-2b in Altum’s patented BiPhasix™ technology. The BiPhasix system uniquely enables efficient delivery of biomolecules across the mucosa.

Interferon alpha-2b is a potent, broad acting anti-viral agent, with established anti-HPV activity. Intron A® is approved for treatment of HPV induced genital warts (condylomata acuminate). Treatment requires intra-lesional injections three times a week. This administration makes it very difficult to use in indications such as HPV-cervical neoplasia, where lesions are not readily visible and the multiple local injections impair patient quality of life on many levels. There is also the cost and inconvenience of repeated healthcare professional visits for the injections. Intron A has therefore not been developed in this indication. Intravenous interferon results in systemic toxicities which precludes its use for treatment of cervical HPV. HPV-cervical dysplasia is a local disease ideally treatment with the local delivery of interferon alpha-2b. The delivery should be easy to use and self-administered at home and safe, without systemic and local side effects). AP-001 is intended to fulfill this need.

AP-001 is a self-administered intra-vaginal cream. It fills the vagina in proximity to the cervix following self- administration. The product’s viscosity prevents vaginal leakage of the cream following administration, thereby allowing prolonged coating the cervix for optimal drug delivery. AP-001 has completed Phase 1 and Phase 2 clinical trials, where it was shown to be active (in cervical neoplasia regression) and safe (no systemic or local side effects). A randomized Phase 2b clinical trial in HPV-cervical CIN2/3 patients is projected to be initiated by Q1 2021.

References:

Clinical Outcome of Topical Interferon Alpha-2b Cream in Phase II Trial for LSIL/CIN 1 Patients – PDF

Stabilization of Interferon alpha-2b in a Topical Cream – PDF

BiPhasix™ Platform

The Challenge: Overcoming the Dermal Barrier

By design, the skin is a formidable barrier to penetration by external agents. In order to reach their target site within the underlying layers of the skin or beyond the skin to the systemic circulation, topical drugs must first penetrate the stratum corneum, the outermost layer of the skin. It is this layer which is considered to be the rate-limiting barrier to drug absorption.
The goal is to have a safe delivery system that does not irritate or damage the skin barrier after repeated usage in patients.

The BiPhasix™ Solution: Altum Proprietary Delivery Platform

Altum is developing its proprietary BiPhasix™ liposomal delivery system which has greatly improved the features of traditional liposomes. In contrast to traditional liposomes that entrap a single, aqueous phase, our system is a complex system where the lipid bilayers entrap both aqueous and oil phases in the form of a stabilized emulsion.

BiPhasix™ is constructed with multi-compartmental lipid vesicles. BiPhasix™ makes it possible to achieve greater formulation versatility than previously attainable with traditional creams, gels or ointments – or even conventional liposomal delivery systems. Thus, BiPhasix™ dermal delivery system combines the advantages of liposomes and micro-emulsions, offering a wider range of formulation options for a variety of drug substances:

  • – Water soluble compounds
  • – Lipid soluble compounds
  • – Proteins
  • – Peptides
  • – Plasmids

The lead product from the BiPhasix™ platform is AP-001.

OUR LEADERSHIP TEAM

BetterLife has assembled a highly experienced management team that has clinical, commercial, product development and financial experience

Breaking News

May 12, 2020 The Globe and Mail

Interferon Emerges as Potential Treatment For COVID-19

May 11, 2020 Medscape

Triple Antiviral Combo May Speed COVID-19 Recovery

May 11, 2020 CISION PR Newswire

BetterLife Pharma Highlights Results from Recent Clinical Reports…