The American College of Medical Genetics and Genomics (ACMG) has recently published two statements on the clinical application of polygenic risk scores:

1. The clinical application of polygenic risk scores: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG) (1).
2. Laboratory perspectives in the development of polygenic risk scores for disease: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG) (2).

The ACMG offers a thorough discussion of points to consider in the clinical application of PRS. Antegenes strongly welcomes this initiative by the eminent organization of leading professionals in the field and sees these documents as a crucial step on the path toward the establishment of generally accepted best practices and guidelines necessary for wide-scale clinical uptake of the PRS technology. We find that the considerations by ACMG are in excellent alignment with the guiding principles followed at Antegenes for the development and use of our polygenic risk score tests. Antegenes agrees with all points but wishes to clarify that we have already considered these circumstances, spent considerable effort to address them and found and applied solutions to them. We consider all the raised issues highly relevant and address each one below.

Points to consider for the clinical application of polygenic risk scores by ACMG and Antegenes’ responses:

1. PRS test results do not provide a diagnosis, instead, they provide a statistical prediction of increased clinical risk.

• Antegenes clarifies in its test information that PRS tests cannot be used to diagnose cancer (e.g., “AnteBC test cannot be used to diagnose breast cancer”).

2. A low PRS does not rule out significant risk for the disease or condition in question.

• PRS is a separate independent risk factor that characterizes one component of hereditary risk for a disease. Each disease has other risk factors that can affect the development of tumours to varying degrees. PRS operates with disease risk probabilities offering clear risk differences, not with categorical statements. Therefore yes, PRS should be used in a relevant clinical context with other risk factors. In tests’ information Antegenes always states, for example:“High risk does not necessarily mean that the patient will develop breast cancer during her lifetime.”“Moderate or lower risk does not necessarily mean that the patient will never develop breast cancer during her lifetime.”“The results of this test should be applied in combination with other relevant clinical data. In addition to genetic predisposition, other risk factors influence the risk of developing breast cancer.”

3. If the risk prediction of a PRS is derived from a population that is different from the patient being tested, then the results may have a poor predictive value for the patient.

• Yes, the ethnic background should be considered. Antegenes has made analyses about PRSs performance based on the UK Biobank’s different ethnic groups data and has implemented relevant adjustments for PRS test results. Antegenes’ genetic testing process always includes specification about an ethnic group of an individual.

4. Isolated PRS testing is not the appropriate test for clinical scenarios in which monogenic etiology is known or suspected.

• We agree that monogenic and PRS testing should be complementary and PRS testing without considering the possible presence of monogenic pathogenic variants is not appropriate. Antegenes always recommends also monogenic pathogenic variant testing, at least considering cancer monogenic pathogenic variant testing criteria and relevant clinical guidelines implemented in the specific country (3-7).

5. Before testing, a patient and provider should discuss the indications for the PRS test, and the patient should be informed how the PRS results will be used to guide medical management.

• We agree that for PRS testing it is necessary to give full information about the PRS test, its testing purposes, its limitations of use, but also possible clinical recommendations.

6. PRS-based medical management should be evidence-based; however, there is currently limited evidence to support the use of PRS to guide medical management.

• We fully agree that PRS-based medical management should be evidence-based, but we emphasize that there is already sufficient evidence for the implementation of risk-stratified cancer prevention. There are clinical guidelines for implementing risk-based prevention in breast cancer (3, 8, 9), colorectal cancer (6, 10, 11), and prostate cancer (7, 12-15), using information from monogenic pathogenic variant testing and other clinical factors. PRS as an independent risk factor gives a similar level of risk estimations in comparison with moderate risk monogenic pathogenic variants. On the other hand, it can be argued that not considering the effect of PRS in the assessment of hereditary cancer risk in the absence of monogenic pathogenic variants gives an individual an incomplete risk assessment and is no longer the best modern clinical practice.

7. Clinical follow-up for PRS should be consistent with best practices outlined by professional societies with appropriate expertise in instances when and where evidence-based practice guidelines exist.

• Antegenes concurs and has developed clinical recommendations based on PRS risk levels using the information about available evidence-based professional guidelines and into the context of these guidelines.

8. The ACMG’s position is that preimplantation PRS testing is not yet appropriate for clinical use and should not be offered at this time.

• Antegenes agrees and offers PRS tests for age groups where PRS risk estimations give clinically meaningful information for risk-stratified clinical recommendations about cancer type-specific prevention and screening.

Key Learning Points from ACMG:

At this time, the ACMG advocates against clinical implementation of PRS testing unless the provider and patient have a clear understanding of the limitations of the testing and applicability to the specific patient, including how the results will be used to guide evidence-based clinical care. 

Antegenes’ comment:

We agree. Antegenes has considered all described limitations and has created solutions to these including relevant information, and also has created clinical recommendations for different PRS risk levels based on available evidence for prevention and screening of specific tumour types.

References:

1. Abu-El-Haija A, Reddi HV, Wand H, Rose NC, Mori M, Qian E, et al. The clinical application of polygenic risk scores: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023:100803.
2. Reddi HV, Wand H, Funke B, Zimmermann MT, Lebo MS, Qian E, et al. Laboratory perspectives in the development of polygenic risk scores for disease: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genetics in medicine : official journal of the American College of Medical Genetics. 2023:100804.
3. Sessa C, Balmana J, Bober SL, Cardoso MJ, Colombo N, Curigliano G, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline. Ann Oncol. 2023;34(1):33-47.
4. Wappenschmidt B, Hauke J, Faust U, Niederacher D, Wiesmuller L, Schmidt G, et al. Criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for the Classification of Germline Sequence Variants in Risk Genes for Hereditary Breast and Ovarian Cancer. Geburtshilfe Frauenheilkd. 2020;80(4):410-29.
5. Personaalmeditsiini kliinilised juhtprojektid rinnavähi ja südame-veresoonkonnahaiguste täppisennetuses. https://www.etag.ee/wp-content/uploads/2021/07/Lõpparuanne.pdf.
6. Stjepanovic N, Moreira L, Carneiro F, Balaguer F, Cervantes A, Balmana J, et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2019;30(10):1558-71.
7. Russo J, Giri VN. Germline testing and genetic counselling in prostate cancer. Nat Rev Urol. 2022;19(6):331-43.
8. NICE. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer 2019 [NICE Clinical guideline [CG164]]. Available from: https://www.nice.org.uk/guidance/cg164/chapter/recommendations#breast-cancer-risk-category.
9. Rhiem K, Auber B, Briest S, Dikow N, Ditsch N, Dragicevic N, et al. Consensus Recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer. Breast care (Basel, Switzerland). 2022;17(2):199-207.
10. Helsingen LM, Vandvik PO, Jodal HC, Agoritsas T, Lytvyn L, Anderson JC, et al. Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline. BMJ. 2019;367:l5515.
11. Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut. 2020;69(3):411-44.
12. American Cancer Society Recommendations for Prostate Cancer Early Detection. 2019.
13. Gandaglia G, Albers P, Abrahamsson PA, Briganti A, Catto JWF, Chapple CR, et al. Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019. Eur Urol. 2019;76(2):142-50.
14. Van Poppel H, Roobol MJ, Chapple CR, Catto JWF, N’Dow J, Sønksen J, et al. Prostate-specific Antigen Testing as Part of a Risk-Adapted Early Detection Strategy for Prostate Cancer: European Association of Urology Position and Recommendations for 2021. Eur Urol. 2021;80(6):703-11.
15. Van Poppel H, Hogenhout R, Albers P, van den Bergh RCN, Barentsz JO, Roobol MJ. A European Model for an Organised Risk-stratified Early Detection Programme for Prostate Cancer. Eur Urol Oncol. 2021;4(5):731-9.

The Estonian health technology company Antegenes has raised 2.3 million euros in funding to bring its innovative genetic tests for personalised cancer prevention into wider use in healthcare, scale the team and expand to new foreign markets. Funding was received from investors, Enterprise Estonia and the European Institute of Innovation and Technology.

Antegenes’ novel genetic tests assess patient’s personal cancer risks and include clinical recommendations for further personalised cancer prevention. Tests are based on innovative polygenic risk score technology which helps to clarify individual’s genetic predispositions to cancer. It therefore allows for more accurate prevention and early detection measures – crucial in the fight with cancer. The tests are currently used to determine the genetic risk to four cancers: breast cancer, prostate cancer, colon cancer, and skin melanoma.

Antegenes raised 1.6 million euros from investors in seed round, which was led by Pipedrive co-founder Timo Rein, Pipedrive’s first investor Peep Vain and entrepreneurs Aare Kurist and Andreas Henn Otsmaa. In addition, other Estonian investors and entrepreneurs participated in the round. The financing round was advised by investment banking company Keystone Advisers and law firm Sorainen.

“The investments make it possible to bring personalised cancer prevention into wider use in healthcare, including in new markets. In addition to Estonia and the United Kingdom, we have started operations in Sweden, Norway, Portugal, and Spain. In the coming months we will also enter the German market,” said Dr. Peeter Padrik, founder and CEO of Antegenes. “To reduce cancer deaths, the genetic predisposition of cancer should be analysed for all people, and our vision is to implement this internationally with our partners. This is why the current investment round is very important for our growth and next steps. We are glad that investors share our vision of the future of healthcare.”

“Antegenes team has been working for a number of years to help people identify and prevent some of the most difficult chronic conditions all of us are potentially subject to during our lifetime. Of course, to realize such a vision one needs to overcome enormous challenges, and we want to support the team as it tackles them. It takes many years to build a great business – and similarly, create a lasting health change – and we believe the current milestone gives a boost to Antegenes team to take some exciting steps towards their future,” added lead investor Timo Rein.

In addition, Antegenes has received two grants to bring research-intensive innovation to international healthcare. The first is the BRIGHT project, which is financed with 2.28 million euros by EIT Health, of which 500,000 euros is a grant to Antegenes. At the centre of the project is Antegenes and the breast cancer genetic risk test AnteBC. The goal of the project is to implement the AnteBC test in breast cancer precision prevention in Estonia, Portugal and Sweden, with further developments in Europe more broadly. By enabling precision prevention with targeted screening, BRIGHT promises to improve patient outcomes and significantly reduce breast cancer mortality. The partners of the project are the University of Tartu, IESE Business School, Tartu University Hospital, Estonian Health Insurance Fund, Uppsala University Hospital, North Lisbon University Hospital Centre, and GE Healthcare. EIT Health, part of the European Institute of Innovation and Technology, is a network of the best healthcare institutions in Europe, supporting the development of the most promising start-ups and business concepts.

The second grant came from the Norway Grants Green ICT programme, which supports business cooperation between Estonia and Norway. The goal of the 200,000-euro funding is to implement the breast cancer genetic risk test AnteBC as part of a breast cancer screening routine in Norway. The partners of the project are the University of Oslo, Oslo University Hospital, Vestre Viken Hospital Trust, and Oslo Cancer Cluster. All partners have a strong scientific and clinical background and are acknowledged institutions in the field of oncology both in Norway and internationally.

Antegenes’ products are based on peer-reviewed international research and have been evaluated and validated using anonymous population data of the Estonian Biobank and UK Biobank.

Antegenes is an Estonian health technology company and medical laboratory founded in 2018 with a goal to develop and implement advanced genetic tests based on polygenic risk scores technology for precision prevention of major complex diseases. Antegenes is an official spin-off company of the University of Tartu.

The theme of World’s Fair Expo Dubai 2020 is “Connecting Minds, Creating the Future”, emphasising how we all have the power to build a better world and shape the future. With this in mind, Antegenes was proud to organize a business seminar, where we discussed how to implement innovative genetic information into cancer precision prevention with the goal to help people live longer and healthier lives.

It was an immense honour to welcome in our panel:
Dr Fatima Alkaabi, the Director of the Genome Office in Abu Dhabi Executive Office (UAE),
Ms Jumana AlAzazi also from the Genome Office (UAE) and
Dr James Mackay, Medical Director of Everything Genetic Ltd (UK).

The panel was moderated by Antegenes CEO & Founder Dr Peeter Padrik.

“Our discussion with Dr Fatima Alkaabi and Dr James Mackay confirmed that United Arab Emirates, United Kingdom and Estonia all have the same visions for genetics-based personalized prevention of cancers and other common diseases, and have already taken the first steps for integrating genomic medicine into healthcare. We acknowledged, that we need collaboration among stakeholders from different countries to support and ensure that the best genetics-based innovative solutions and screening programs are integrated in healthcare systems globally,” said Dr Peeter Padrik after the event.

The business seminar titled “Digital nation. Personalized solutions for healthcare & wellbeing” took place on 31st of January, and was organized by Antegenes and the City of Tartu, both official members of the Estonian Pavilion.

Other panels focused on digital health solutions and changes and challenges in the molecular diagnostics. Companies in the Estonian health-tech delegation taking part of the seminar were Asper Biogene, Competence Centre on Health Technologies, Connected Health Cluster, DocuMental, Institute of Genomics at the University of Tartu, Migrevention, Nordwise Biotech, Solis BioDyne, Tartu Biotechnology Park, and Triumf Health.

As one of the companies of the Estonian health business delegation, Antegenes also met with representatives from the United Arab Emirates (UAE) Ministry of Health and Prevention and the Abu Dhabi Department of Health to discuss opportunities for cooperation. Dr Padrik commented on the opportunities existing between the two countries: “Similar to Estonia, one of the important goals of the health care system in the United Arab Emirates is the personal prevention, diagnosis, and treatment of diseases. A common element definitely shared with Estonia is establishing a nationwide genome project and implementing digital health care opportunities to create a better system.”

Antegenes was supported by Connected Health Cluster and Enterprise Estonia.

The Estonian health technology company Antegenes has raised 500,000 euros and signed a long-term strategic partnership agreement with UK-based healthcare company Everything Genetic Ltd to implement Antegenes genetic testing service in the United Kingdom healthcare system.

Antegenes’ novel genetic tests assess patient’s personal cancer risks and include clinical recommendations for further personalised cancer prevention. Tests are based on innovative polygenic risk score technology which helps to clarify individual’s genetic predispositions to cancer and allows for more accurate prevention and early detection measures. The tests are currently used to determine the genetic risk to four cancers: breast cancer, prostate cancer, colon cancer, and skin melanoma.

Everything Genetic is a leading distributor of market-leading genetic test brands into the UK market, with the aim to democratise genetic testing to healthcare providers and patients for detection, diagnosis and treatment of cancer, cardiac and other illnesses.

“We are very excited for our strategic partnership with Everything Genetic for the wider application of our tests within the UK healthcare sector. This is a historic step as we enter a new era of personalised cancer prevention. Most importantly, we have a clear shared vision of how innovative genetic solutions can help save lives and reduce the impact cancer has on our society,” said Dr. Peeter Padrik, CEO and founder of Antegenes.

Everything Genetic’s CEO, James Price, says the Antegenes investment, into polygenic risk testing technology, can vastly improve patient outcomes for those likely to develop cancers. “Genetic testing for cancer has until now been the preserve of an exclusive few, only available in private clinics with costs running into the thousands, but this new investment into the Antegenes service will deliver a cost-effective way to bring down the cost of this novel tech.“

Dr James Mackay, medical Director at Everything Genetic explains cancer is a disease heavily influenced by genetics. “Although it’s long been understood that genetics plays a part in predisposition to the cancer, this technology gives proven data to demonstrate just how significant a role an individual’s genes might play in the likelihood of them developing cancer. And the earlier we can spot that and take preventative measures, the better.“

“Antegenes tests truly have the potential to turn the old trope of prevention being better than the cure on its head, in identifying predisposition to certain conditions even before prevention. It demonstrates an exciting step in the advancement of life sciences and we really can’t wait to see how the technology impacts individual patients’ outcomes across the UK,” added Dr Mackay.

„For us it’s important that our innovative solutions are trusted by top UK clinicians so we can start implementing personalised cancer prevention at a large scale. This new investment will be also used to further expand our testing service into new markets in Europe,“ added Dr Padrik.

The Antegenes tests can improve patient outcomes for those more genetically predisposed to certain cancers and other complex diseases. The firm claims the quick five-minute saliva tests will “democratise” the use of the polygenic risk-based genetics testing for individuals, healthcare professionals and organisations, helping to deliver more cost-effective patient outcomes, whilst increasing the chances of preventing and surviving cancer.

Antegenes’ products are based on peer-reviewed international research and have been evaluated and validated using anonymous population data of the Estonian Biobank and UK Biobank. The data from Antegenes’ tests provide three actionable data points for patients, including: absolute risk of developing the specific cancer over the next decade, general population comparison against people the same age, and relative comparison of your risk versus that of the general population.

Antegenes is an Estonian health technology company and medical laboratory founded in 2018 with a goal to develop and implement advanced genetic tests based on polygenic risk scores technology for major complex diseases.

Antegenes is proud to appoint its first advisory board member Akshay Mody, who brings his expert advice and guidance as a medical leader, in order to help us successfully develop and launch our innovative products in healthcare.

Akshay Mody has spent over 20 years in the healthcare industry. His most recent experience is in overseeing the rapid growth of the medical organisation Viiv Healthcare as Chief of Staff, which successfully concluded 7 Phase 3 trials (resulting in 4 NDAs) and established a portfolio of Discovery and Early Development products in just 5 years. This has given him a unique understanding of managing successful short- and long-term objectives in parallel with expansion. This experience, linked to his earlier roles leading multifunctional teams in global and European launches for assets at GlaxoSmithKline, launching breakthrough specialist drugs in multiple therapy areas as a Regional and Country General Manager (at Roche, Novartis and Ciba-Geigy) will allow our executive management team of Antegenes to have the support we need at this important stage of growth.

With the establishment of the advisory board, our intention is to identify a group of people who have vast experience in their respective fields. The board’s mission is to provide our executive team objective judgement that is critical to us in establishing our identity, footprint and ultimately fulfilling our mission to empower individuals, medical professionals and public healthcare in using genetics for personal and public health activities.

Our advisory board members will provide us unbiased advice in areas such as strategy, performance, sustainability, resources, transformation, diversity, standards of conduct and evaluation of performance. We believe this will help guide, improve and evolve our corporate credibility and governance standards and also manage risks while focusing on bringing our solutions to patients and healthcare providers.