Rezafungin (Formerly CD101 IV)

Rezafungin (CD101 IV) Overview

Rezafungin is a novel molecule in the echinocandin class of antifungals, considered to be the safest class of antifungals. It is a broad spectrum, long-lasting echinocandin with demonstrated potent in vivo activity against representative strains of:

  • Candida spp.
  • Aspergillus spp.
  • Pneumocystis spp.
  • Trichophyton mentagrophytes
  • Trichophyton rubrum
  • Microsporum gypseum

Rezafungin is being studied to address unmet needs in:

Current treatment alternatives for systemic fungal infections, including polyenes, azoles, and currently-approved echinocandins, have significant limitations. Toxicities, drug-drug interactions, low or variable exposure, daily intravenous administration and increasing resistance, are all issues which complicate therapy today in patients who are already inherently complex and very ill. Rezafungin offers a potential new solution for patients and clinicians to solve for these significant limitations.

Rezafungin has a prolonged half-life and front-loaded plasma exposure which, in contrast to all other echinocandins, allows for once-weekly IV therapy. This pharmacokinetic profile may overcome limitations of the current standard of care. Rezafungin has potential to:

Rezafungin: First Echinocandin with Significant Potential to Penetrate Azole and Bactrim Markets
  • be the only single-agent prophylaxis across several fungal pathogens – Candida, Aspergillus and Pneumocystis, displacing azoles and Bactrim
  • be the only echinocandin to facilitate shorter and less costly hospital stays
  • be the only echinocandin to provide more cost effective and compliant outpatient echinocandin treatment and prophylaxis
  • treat less susceptible pathogens by achieving high human exposures

The U.S. Food and Drug Administration (FDA) has designated rezafungin as a Qualified Infectious Disease Product (QIDP) with Fast Track status and orphan drug designation. The designations are for the use of rezafungin in the treatment of candidemia and invasive candidiasis. The seven-year period of marketing exclusivity provided through orphan designation combined with an additional five years of marketing exclusivity provided by the QIDP designation positions rezafungin for a total of 12 years of potential marketing exclusivity to be granted at the time of FDA approval. We intend to seek QIDP, fast track and orphan drug designations for rezafungin for prophylaxis.

Pipeline

Phase 1

Phase 2

Phase 3

Treatment of Candidemia and Invasive Candidiasis

Phase 3 Planned Mid-2018

65%

Prophylaxis for Candida, PCP and Aspergillus in alloBMT

Phase 3 Planned Mid-2018

65%

Opportunity: Invasive Fungal Infections

Invasive fungal infections (IFIs) are a serious threat to millions of patients around the globe, resulting in more than 1.5 million deaths annually. These infections continue to be a global health issue, especially for critically ill patients in hospitals and patients with compromised immune systems.

Of the most significant IFIs, approximately 90% of related deaths are caused by 4 types of fungi: Candida, Aspergillus, Cryptococcus, and Pneumocystis. Candida species are most common in hospital-acquired infections, while Aspergillus species are predominant in immunocompromised patients. Cryptococcus and Pneumocystis contribute to the significant morbidity and mortality associated with IFI. While the incidence of life threatening Mucormycosis is low, the mortality rates associated with this disease ranges from 30-90%.

We estimate that the annual worldwide sales of prescription systemic antifungals are approximately $4 billion. This includes therapies used as prophylaxis (preventive) in the inpatient and outpatient setting, and therapies used for the treatment of suspected or documented infections in hospitalized patients and patients who have being discharged from the hospital and need continued outpatient antifungal treatment.

Estimated U.S. Deaths in Patients with Hospital Treated Fungal Infections

Incidence & Mortality

Disease (most common species)
Location
Estimated life-threatening infections/year at that location*
Mortality rates (% in infected populations)*
Opportunistic invasive mycoses
Aspergillosis (Aspergillus fumigatus) Worldwide >200,000 30–95
Candidiasis (Candida albicans) Worldwide >400,000 46–75
Cryptococcosis (Cryptococcus neoformans) Worldwide >1,000,000 20–70
Mucormycosis (Rhizopus oryzae) Worldwide >10,000 30–90
Pneumocystis (Pneumocystis jirovecii) Worldwide >400,000 20–80
Endemic dimorphic mycoses*
Blastomycosis (Blastomyces dermatitidis) Midwestern and Atlantic United States ~3,000 <2–68
Coccidioidomycosis (Coccidioides immitis) Southwestern United States ~25,000 <1–70
Histoplasmosis (Histoplasma capsulatum) Midwestern United States ~25,000 28–50
Paracoccidioidomycosis (Paracoccidioides brasiliensis) Brazil ~4,000 5–27
Penicilliosis (Penicillium marneffei) Southeast Asia >8,000 2–75

*Estimates based on available data.

Endemic dimorphic mycoses can occur at many locations throughout the world. However, data for most of those locations are severely limited. These are estimates of infections per year and mortality at a specific location, where the most data are available.

From Brown et al. Sci Transl Med.2012;4:165:165v13. Reprinted with permission from AAAS.

Clinical Program

Phase 3 Planned

Two phase 3 registration trials are planned to start in 2018. The first is an international double-blind randomized trial for the treatment of candidemia and invasive candidiasis. The second is an international double-blind randomized trial for the prophylaxis of Candida, Aspergillus and Pneumocystis in patients undergoing allogeneic bone marrow transplant.

Phase 2: STRIVE

We have completed enrollment in our Phase 2 international trial of rezafungin in the treatment of candidemia and invasive candidiasis called STRIVE.

STRIVE is a Phase 2, multicenter, randomized, double-blind trial evaluating the safety, tolerability and efficacy of rezafungin compared to intravenous caspofungin followed by oral fluconazole therapy (i.e., “step-down” therapy) in patients with candidemia or invasive candidiasis. In two arms of the trial, patients receive either 400 mg of rezafungin once weekly for two weeks or 400 mg for the first week followed by 200 mg once weekly for the second week. For both arms, a third or fourth weekly dose may be administered if medically indicated. In the comparator arm, patients receive caspofungin according to the approved prescribing information. Oral step-down fluconazole therapy can be administered in the comparator arm following IV caspofungin therapy based on medical judgement and if specific clinical and microbiological criteria were met. More than 90 patients have been enrolled in the mITT population in STRIVE across North America and Europe. Data are expected in the first quarter of 2018.

Phase 1

We have completed two Phase 1 clinical trials for rezafungin: a single ascending dose trial (SAD) and a multiple ascending dose (MAD) trial. These studies established the safety and PK profile of rezafungin in healthy subjects, demonstrating that up to 400 mg once weekly for 3 consecutive weeks was safe and well tolerated.

Key results of rezafungin multiple ascending dose trial include:

  • Safely achieved very high front-loaded plasma exposures potentially improving treatment outcomes
  • Long half-life enables weekly dosing
  • Well tolerated across entire dose range
  • No serious or severe adverse events
  • No clinical chemistry, hematology or ECG safety concerns

These data supported the continued development of rezafungin. Additional Phase 1 trials are planned or underway for continued evaluation of safety and drug-drug interactions.

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