Pipeline & Clinical Programs
Oncology Clinical Programs
To maximise clinical and financial value from Veyonda’s versatility, we have two strategic clinical development objectives:
- Establish Veyonda as an essential adjunct to radiotherapy in the treatment of prostate cancer:
- with all forms of radiotherapy,
- across multiple stages of the disease continuum
- Discharge portfolio risk by studying Veyonda:
- in combination with radiotherapy in rare-and-less-common cancers and/or end-of-life settings
- in combination with non-radiotherapy-based treatments such as immune-oncology and/or chemotherapy
Two separate clinical programs are currently underway:
- Direct and Abscopal Response to RadioTherapy (DARRT) Program
- Chemotherapy Enhancement Program (CEP)
Underneath these programs, one study, the CEP-1 study, has been completed and two studies, DARRT-1 and LuPIN, are currently underway
Phase 1, open-label, dose escalation and dose expansion study
24 mCRPC patients
400mg, 800 mg and 1200mg NOX66 + palliative RT
Objectives: Safety & Efficacy
Phase 1, open-label, 36-week Investigator-initiated study
177 Lutetium-PSMA-617 IV + 400 mg daily or 800 mg NOX66 daily for 9 days
Objectives: Safety & Efficacy
Phase 1, open-label, 2 cohort study
19 end-stage patients with multiple tumour types
400mg & 800 mg NOX66 + carbonplatin
Objectives: Safety & Efficacy
Prostate cancer is very common. 1 in 9 American men will be diagnosed with prostate cancer during their lifetime and in Australia it is the most common cancer amongst males and second most common cancer overall1,2. Despite significant advances in the treatment of prostate cancer many men still succumb to this disease. In the United States, prostate cancer is the second leading cause of cancer death in American men and overall about 1 in every 40 men will die from this disease1. A similar pattern is seen in Australia where 3500 men lost their lives to prostate cancer in 20182
The fatality rates are largely due to the most advanced stage of the disease where the cancer has spread throughout the body and is no longer responding to hormonal treatments – metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC have limited survival prospects, with the median survival time being approximately 13 months.3 At the latest stages of mCRPC, palliative radiotherapy may be offered to alleviate the patients’ symptoms but does not offer any curative prospects. In Australia alone an estimated 1400 courses of palliative radiotherapy are administered for prostate cancer every year.4
Sarcomas are a group of rare cancers that develop from cells in the body’s supporting tissues. They are complex malignancies that cannot be cured, once surgical resection is no longer possible. They may be tumors in the “soft tissue” (in the adipose tissue, the muscles or the vessels, but may also be visceral, in the stomach and colon, for example) and in the “hard” parts (bone and cartilage) of the body.5 In the US, each year, 15,000 new sarcoma cases are diagnosed, and 6,000 related deaths are recorded. While sarcoma is a rare cancer in adults (1% of all adult cancers), it represents almost 20% of all childhood cancers for which no therapeutic option exists.6
Surgery is the principal treatment for soft tissue and bone sarcomas, when localized. Chemotherapy and/or radiotherapy are sometimes administered in addition, according to the type of sarcoma, its grade, its location and the results of the surgery.7 Unfortunately, over the last few decades, outcomes for most types of sarcomas have not improved significantly and the standard-of-care treatment for metastatic soft tissue sarcoma remains doxorubicin, which was discovered in 1969.8
What makes enhancement of radiotherapy an attractive opportunity for Veyonda?
- Radiation therapy is a highly effective and commonly used tool in cancer treatment and palliative management9
- About 60% of cancer patients will have RT at some point in their treatment journey10
- Radiation therapy deposits high physical energy radiation on the cancer cells, which directly and indirectly damage DNA9
- The potential toxicity to normal tissue limits the dose of radiotherapy that can safely be delivered to tumour sites11
- NOX66 has been shown to possibly enhance radiation-induced cytotoxicity possibly in a number of cancer cell lines12
The objectives of the DARRT program are to demonstrate that in advanced solid tumours:
- Veyonda plus palliative RT increases efficacy relative to palliative RT alone
- Veyonda plus lower dose RT achieves similar efficacy to standard dose RT
- Treatment with Veyonda plus lower dose RT increases Quality of Life – in late stage disease as well as earlier in the disease continuum
With our first two prostate studies underway, we are progressing confidently towards our first strategic objective. This confidence has been buoyed by preliminary results from our DARRT-1 study.
DARRT-1 is a Phase Ib, multi-centre, open-label dose escalation and dose expansion study in men with metastatic Castrate Resistant Prostate Cancer (mCRPC) is currently ongoing. In this study palliative radiotherapy (20Gy in 5 fractions) is delivered to one lesion, with patients receiving overlapping (concurrent), combination treatment with Veyonda for 15 days. In the dose escalation part of the study, 3 cohorts of 4 men per cohort were enrolled into escalating dose cohorts of Veyonda of 400 mg, 800 mg and 1200 mg, respectively. The 1200 mg dose was then selected by an independent data and safety monitoring board for investigation in the 12 patients to be enrolled into the dose expansion cohort.
Two patients in the 800 mg cohort and 2 patients in the 1200 mg cohort demonstrated a fall in PSA of >50% from baseline to 12 weeks (deemed to be a response). 3/4 patients in the 800 mg cohort and 2/4 patients in the 1200 mg cohort recorded a pain response (>30% reduction from baseline on the Brief Pain Inventory). One patient in the 800 mg cohort had a partial response (as per RECIST v1.1). The 800 mg and 1200 mg cohort each had 3 patients with stable disease (as per RECIST v1.1) at 12 weeks.
Veyonda has been well tolerated and no serious adverse events have been deemed related to Veyonda
LuPIN is an investigator-initiated trial being led by Professor Louise Emmett at St Vincent’s hospital in Sydney. Veyonda is being evaluated for its ability to increase incidence, degree, and durability of response to 177Lu-PSMA-617.13 177Lutetium-PSMA-617 is an exciting potential therapy currently in late phase clinical trials for men with mCRPC.14 It is a radioligand therapy that targets prostate-specific membrane antigen (PMSA) on the surface of prostate cancer cells. It can be delivered as low-dose radiation to all cancer cells within the body via intravenous administration. Efficacy and safety outcomes may be improved by enhancement of radiations effect on tumour cells.
What makes Chemotherapy enhancement an attractive opportunity for Veyonda?
- Chemotherapy is a mainstay in the treatment of numerous types of cancer in all stages of the disease15
- Issues associated with chemotherapeutic agents include toxicity and the development of tumour resistance15,16
- Veyonda’s active ingredient has been shown to be chemosensitising in a range of cancer cell lines12,17-20
The objectives of the CEP program are to demonstrate that in advanced solid tumours:
- Veyonda plus chemotherapy achieves superior efficacy to chemotherapy alone, and/or
- Veyonda plus lower dose chemotherapy achieves similar efficacy to standard dose chemotherapy
Achieving these program objectives will help us to achieve our second strategic objective. We are off to a good start in this regard, as the results of CEP-1 were encouraging.
CEP-1 was a Phase I multi-centre, open-label, non-randomised, study in patients with metastatic solid tumours (breast, prostate, lung, ovarian and head & neck). Treatment consisted of monotherapy lead-in followed by up to 6 cycles of Veyonda in combination with lower-dose carboplatin (50% of standard for cycles 1-3, followed by 75% of standard for cycles 4-6)
Efficacy assessment included overall response according to RECIST v1.1 criteria. Of the 8 patients (2 in the 400 mg cohort and 6 in the 800 mg cohort) who completed 6 cycles of carboplatin in combination with Veyonda (on days 1-7 of each cycle), 1 patient (in the 800 mg cohort) had a partial response, 5 patients had stable disease (1 patient in the 400 mg cohort and 4 patients in the 800 mg cohort) and 2 patients had progressive disease (1 patient in each dose cohort). Veyonda was well tolerated and only 1 adverse event, anaemia, was considered to be related to Veyonda.
Of the 9 patients allocated to the higher dosage (800 mg) of Veyonda®, 5/9 (56%) showed stable disease (no tumour growth and no new tumours) or a partial response (up to 99% shrinkage of measurable lesions) over the 8-month term of the study. The Company and its medical advisors regard this outcome as significant, given that all patients were heavily-pretreated and with extensive and progressive Stage 4 chemo-resistant disease.
- American Cancer Society (https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html)
- Cancer Australia. (2018). Statistics. Retrieved from Prostate Cancer: https://prostate-cancer.canceraustralia.gov.au/statistics
- Moreira DM et al. 2017. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer; 15(1): 60–66.
- (2017, 08 02). Radiotherapy in Australia 2015-16. Retrieved from Australian Institute of Health and Welfare: https://www.aihw.gov.au/getmedia/93ee58ce-2ad1-49fe-86e3-f552ff6ab54c/20730.pdf.aspx?inline=true
- Sarcoma Foundation of America: https://www.curesarcoma.org/
- Gao, P et al. 2018. Advances in sarcoma gene mutations and therapeutic targets. Cancer treatment reviews, 62, pp 98-109.
- Cassinelli, G. (2016). The Roots of Modern Oncology: From Discovery of New Antitumor Anthracyclines to Their Modern use. Tumori Journal, 102, 226-235
- Baskar R, et al. Front Mol Biosci. 2014;1:24
- Radiation therapy and you. 2016. Available at: www.cancer.gov/publications/patient-education/radiationttherapy.pdf. Accessed April 2019.
- Citrin DE, et al. Semin Oncol. 2014;41(6):848-59
- Data on file.
- Trial registration number ACTRN12618001073291. Available at: www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374100. Accessed March 2019.
- Bräuer A, et al. Eur J Nucl Med Mol Imaging. 2017;44(10):1663-1670
- Rumpold H & Wimder T. Magazine of Eur Med Oncol. 2017;10:119-120.
- Gupta S, et al. Ann N Y Acad Sci. 2011;1215:150-60.
- Alvero et al. Cancer Biol Ther. 2007;6:612-7.
- Yao et al, 2012. Mol Oncol. 2012;6:392-404.
- Li et al. Cell Biochm Biophys. 2014;70:1337-42.
- Brown et al. Drugs Future. 2008;10:844-60
NOXCOVID Clinical Program
NOXCOVID-1 is a Phase 1 dose-escalation and dose-expansion study focusing on safety and proof-of-principle endpoints (biomarker and clinical responses). It will be in up to approximately 40 patients who have been admitted to hospital for respiratory insufficiency (not requiring artificial ventilation) associated with the SARS-CoV-2 virus. UK-based contract research organisation, Clinical Accelerator, has been appointed to oversee the trial, and Australian company, Datapharm, will process the data. A clinical protocol has been designed acting on the advice of Australian, U.S. and European clinicians, and incorporating FDA guidance.
Veyonda is intended for patients with early-stage respiratory disease who are at risk of developing a cytokine storm and septic shock. The aim is to prevent the onset of the cytokine storm that inflicts tissue damage in the lungs and other major organs. Veyonda is not intended to replace other potential treatments like dexamethasone that may provide a clinical benefit in patients with more advanced disease already experiencing a cytokine storm.
Subject to regulatory approvals, NOXCOVID-1 will be conducted at a number of sites in Ukraine and Moldova, where there is a rising number of COVID-19 cases and deaths as the pandemic moves eastward across Europe.
The process of obtaining regulatory approval for the trial from central regulatory authorities and local hospital ethics committees is underway. Ukraine has an expedited COVID-19 clinical trial approval process.