To read who we are and what to expect out our newsletter refer to the WELCOME post.

Few reflections for the past year…

One year ago, the first High Risk High Returns note went out to a few hundred inboxes, quickly followed by the first catalyst preview. The promise was simple. Read biotech clinical catalysts the way the people who actually move these stocks read them. With a clear view, a clear prediction, with solid scientific/clinical foundation and a realistic financial/investing understanding. Twelve months later, you’re still here. And there are a lot more of you. We’ve grown to to 600+ readers.

Few takeaways:

• Haven’t regretted it

• Thankful for the interest

• Enjoyed every minute of it

• Impressed with the results

• Excited about what’s to come

• Surprised with the level of engagement

• Overwhelmed with the number of ideas

• Curious about upcoming clinical readouts

• Happy that the portfolio tracker if finally released

• Bullish about Lp(a)/Novartis, Abivax, Rapport, Amylyx

Early adopters on the platform did the best. Writers like Heather Cox Richardson and Matthew Yglesias arrived early and earned millions. But as more writers showed up the subscription revenue pie didn’t grow commensurately. Even with Substack’s discoverability mechanism (something that is missing on places like Ghost and Beehiv) it was getting more difficult to establish a real career here. - From: The Real Reason that Substack is Collapsing

I could see how early Substack newsletters were able to quickly build a massive following simply as they captured a large market share of the early pool of readers. I wish I was one of the early joiners, but I only started Substacking in mid-2025. I also do not know these specific creators enough to know how they may have reached that — for many - enviable status.

Upon further thinking, I struggled to fully accept the notion that hope is completely lost for anyone joining the platform as a creator, several years after its launch. Especially after seeing first hand, multiple accounts in my niche (finance, investing, biotech) or outside of that - creating their own communities within few months. Even taking a look at my own progress, I would say I was massively impressed and surprised, let alone by the achievements of accounts I admire such as: Biotech Compass, Big Pharma Sharma and others.

Have I reached a point where my Substack channel has become the primary career? Likely not.

Is that completely unlikely to ever happen? Most likely (and hopefully not).

Recent developments, since turning my channel to ‘paid’ have far exceeded my expectations, with more than 20 actual paid subscribers endorsing my ideas and writing - in just 3 months (and 12 months since starting to write for free).

And this is for a ‘gig’ that has been taking mostly (some of) my weekend free time, with posting sometimes being regular and other times less frequent. It makes you wonder, what would focusing full time on this yield 1 year later?

Judging from highly successful examples of peers writing finance and investing: a community of 10s or 20s of thousands of subscribers is not wishful thinking, but mathematically achievable - as long as one keeps going!

Is it possible that money is shifting away from other platforms (such as mainstream media) to ones like Substack and Spotify. There are certainly trends supporting that idea. This is in tandem with a significant mentality and cultural shift in the way people engage with news, education, opinion, and advice.

Job market shifts are also at play here. Many professionals in my industry have left big corporate jobs in highly regulated environments such as banking and have become their own boss, taking all the risk and all the gains as individual creators. The jury may still be out as to whether financially that was a ‘good’ move. But how would one judge that? Based on income generated…? What about one’s ability to be the only decision-maker of how they use their creative abilities and their own time..? For me, leaving my own corporate comfort, at the risk of losing a good income, I was able to gain my time back, which for a while was priceless.

The TAM* does not disappoint, even if competition is fierce

*Total Addressable Market

Taken from:

The Private Ledger

The Numbers Don’t Show a Substack Collapse

Last week I read a thought-provoking piece that has gone viral on Substack recently. In it, the author - Scott Carney, argued that Substack “will collapse” and will no longer be a viable option for writers looking to generate significant income. While I enjoyed reading the piece and resonated with parts of it, I wanted to write a counter argument. A pi…

Read more

10 days ago · 124 likes · 72 comments · The Private Ledger

Set the niche aside for a second.

Substack is one of the fastest-growing media platforms in the world. Among the top 50 English-language news sites, only a handful grew at all last year and Substack grew by roughly 40%, while the field averaged low single digits and most sites shrank outright. Paid subscriptions have doubled, then doubled again, then once more; the last public milestone was 5 million. And the disposable-income argument that readers are simply being priced out doesn’t survive the actual numbers, which have risen, not fallen, since Substack crossed its first million paid subscribers. More writers are joining, so competition is brutal. True. But brutal competition is what a growing market looks like, not a collapsing one. Those are not the same thing.

Note to self: what if I translated my notes to other languages?

The overall trends on Substack are promising - I will let me peer do the backing up here…see below article:

The Private Ledger

The Numbers Don’t Show a Substack Collapse

Last week I read a thought-provoking piece that has gone viral on Substack recently. In it, the author - Scott Carney, argued that Substack “will collapse” and will no longer be a viable option for writers looking to generate significant income. While I enjoyed reading the piece and resonated with parts of it, I wanted to write a counter argument. A pi…

Read more

10 days ago · 120 likes · 66 comments · The Private Ledger

For someone putting out investment content, it is important to note that the big investment banks charge institutional investor clients $1000 / hr to get them on a call and share advice on top stock picks.

Why can’t Substackers have the same opportunity to do so? That’s my first question…although I can understand that regulation is part of the answer.

The thesis is simple, and that’s part of why it landed. Scott Carney argues the subscription model can’t hold: readers have finite money and finite attention, and eventually the newsletters lose. When budgets tighten, your favourite writer takes a backseat to groceries. But this may be irrelevant in the field of finance, where (1) different ball-game of budgets exist; (2) ROIs are many (many) multiples of what a Substack subscription may cost.

Second question would be, why couldn’t institutional investors (VCs, private equities, asset managers, pension funds etc etc) allocate 1% of the millions they pay banks for financial advice, to credible, professional, Substack-based financial/investment content creators.

On the ROI argument I made earlier: I write about biotech catalysts (binary clinical readouts, PDUFA dates) the moments where a stock doubles or halves overnight. Readers are paying for ideas, for edge, for conviction. And that is worth something to a lot of people. Read my recent post where we made our portfolio/ideas tracker available to all our paid readers.

I do get friends and family ask me for biotech stock ideas - ALL the time. And it’s really never that simple (except in the case of …maybe this one, I will always recommend no matter what). There is nuance; there is levels of confidence; there is timing and there is risk. All these cannot be collapsed into one single-word stock recommendation…

Community is real…in ways I never imagined

Here’s what the doomsday view misses. The Substack community brought me in touch with people I would never imagine I could have a connection with:

The reader’s side is even simpler

For a reader, the asymmetry is almost absurd. A year of expert biotech analysis costs less than a single share of most of the stocks it covers. One avoided catalyst blow-up covers a decade of subscriptions. Demand for that isn’t softening in my eyes, at least.

Imagine $AMLX: Stock is up 100% since my August publication - my first publication ever. Even that one - when I only had 50 followers and was still in the unpaid mode, compelled at least one reader who came across my LinkedIn post to donate $50. Possibly they made some money out of that trade recommendation, or possibly they liked my analysis. Who knows? Point is: I put out decent content, marketed it to my audience (Substack, LinkedIn etc); most people ignored it or rejected, but a handful appreciated it. Rinse and repeat is fine for me, thank you.

So, no

Substack isn’t collapsing. Not in finance, where good or even average investments have a clear, calculable return.

One final note: if you write in this niche and it’s been a slow year, the market didn’t shrink. It got harder to fake. Build the record. The readers who pay for edge aren’t going anywhere.

That’s the entire logic behind what I do here…one year after starting my newsletter, one year after leaving a cushy corporate job - no regrets; just perseverence doing what I enjoy.

Stay tuned — Thanks for reading — Systima Capital

Read more

Disclaimer at the end of this post

In less than a year, High Risk, High Returns (Biotech Investing Newsletter) has grown to 600+ subscribers - twice having made it to the top 100 fastest-growing finance pages on Substack.

Along the way, we have made friends and met collaborators with whom worthwhile ideas have been exchanged, enriching our content and improving our calls.

Our portfolio has grown 100% with a catalyst prediction success rate of 80%+.

We’re only just beginning.

The vision is to embed portfolio tracking capabilities for users at the different access tiers to help you understand where, how and when we place biotech bets.

A lot of this is completely free, with additional levels of access provided to those who are interested going a step further.

80% of the members have joined in the past 4 months, and 100% of the paid members have joined in the past 3 months.

So, we wanted to make sure new and old joiners have a clear idea of what this Substack newsletter can give you! Also, whether you’re a free subscriber exploring SystimaCapital’s methods, or considering becoming a paid member looking for the full ‘'suite’ - this post is for you.

Quick tip: Bookmark this page on your browser and download the Substack app for full user experience!

Ideas that succeeded and we still believe in (as of 8th August 2026)

• - Post #02: Catalyst Deep Dive: Amylyx Pharmaceuticals (my full clinical & financial take)

• - Post #06: Stock Deep Dive - Rapport Therapeutics (FOMO is big on this one...)

• - Post #10: Akero Therapeutics ($AKRO) acquired by Novo Nordisk ($NOVO)

• Post #13: How to Play The AI-drug discovery theme as a biotech investor (Pt. 1); AI drug discovery primer, key themes & catalysts in the next 12 months

• Post #17: AtaiBeckley ($ATAI): A discussion with the CEO of a Psychedelics Powerhouse - acquired by $LLY

• Post #21: Novartis’ ($NOVN) Lp(a)-targeting pelacarsen (HORIZON) has to be the most anticipated catalyst for 2026 in cardiology

• Bullish!!! No post written, but plenty of due dilligence performed separately. (We entered right after the cancer ‘signals’ drove the stock down in a single day. We are up 100% since then)

• No post written, but plenty of due dilligence performed separately on their ITK inhibitor and broad potential across indications.

• No post written, but plenty of due dilligence performed separately

Investment Approach

Every piece gets a conviction rating and a clear directive; no hedges. If the case is weak, we say pass. If the setup is strong, we say why and what could break it. Sell-the-news risk gets flagged explicitly, because good data and a good stock move are two different things.

We go deep on every catalyst from a scientific, commercial, financial POV and spend time to understand what the market is thinking, where the ‘puck’ is going to move to and we build short and long term conviction, flagging it accordingly for our readers!

Upcoming Features

We plan to make our portfolio selection process more transparent and more actionable for all readers to understand how we prepare, research and action our trades.

Stay tuned!

SystimaCapital

Leave a comment

Next Catalyst Ideas

• Mirum’s HDV readout in H2’26

• Enanta (see STAT6-targeting asset)

• Satellos (DMD data H2’26)

• Kymera (see STAT6 P2b Atopic Dermatitis data YE26)

• …and more

Disclaimer

High Risk High Returns (”HRHR,” “the Newsletter”) is published by Systima Capital. This Disclaimer applies to all Content published on this Substack, on affiliated social channels (including LinkedIn), and in any related communications, unless expressly stated otherwise.

1. General Informational Purpose Only

The Content published in this Newsletter — including articles, catalyst previews, deep dives, post-data reactions, catalyst calendars, charts, commentary, and any related distribution assets — is provided for general informational and educational purposes only. It is intended to help readers understand clinical, regulatory, and competitive dynamics in the biotechnology and pharmaceutical sectors. It is not, and should not be treated as, a substitute for independent research or professional advice.

2. Not Investment, Financial, Legal, or Tax Advice

Nothing in this Newsletter constitutes investment advice, financial advice, trading advice, legal advice, tax advice, or any other form of professional advice. No Content should be construed as a personal recommendation to buy, sell, hold, or otherwise transact in any security, investment product, or asset, including but not limited to the equity, debt, or derivatives of any company discussed. References to specific tickers, companies, catalysts, or trial outcomes are illustrative and analytical in nature, not recommendations of suitability for any individual reader.

3. No Advisor-Client or Fiduciary Relationship

Systima Capital, Manos Mastorakis, and any contributors to the Newsletter are not registered as investment advisers, broker-dealers, or financial planners with the U.S. Securities and Exchange Commission, the UK Financial Conduct Authority, or any other regulatory body, unless explicitly stated. Reading, subscribing to, or engaging with this Newsletter does not create an advisory, fiduciary, or client relationship of any kind. No duty of care is owed to any reader by virtue of their access to the Content.

4. Author Background Is Not a Basis for Reliance

The author holds a PhD in Genetics and an MSc in Finance, and has prior sell-side and buy-side experience. This background informs the analytical framework applied to Content but does not qualify the author to give personalized investment advice, does not constitute a professional certification recognized by any regulator for that purpose, and should not be relied upon as such. Scientific or financial credentials do not eliminate the inherent uncertainty of the subject matter covered.

5. Biotechnology-Specific and Clinical Catalyst Risks

Biotechnology and pharmaceutical investing carries risks that are materially different from, and often greater than, those associated with more established sectors. Readers should understand and independently evaluate the following before making any investment decision:

• Binary outcome risk. Clinical trial readouts, FDA (or other regulatory) decisions, and PDUFA events are binary in nature. Outcomes can result in a total or near-total loss of value in the underlying security, regardless of pre-event analysis, consensus expectations, or historical base rates.

• Clinical trial limitations. Topline, interim, and preliminary data may not reflect final results. Trial design (endpoints, statistical powering, population selection, open-label vs. blinded design) materially affects interpretation. Statistical significance does not guarantee clinical significance, regulatory approval, or commercial success. Small sample sizes and early-phase data carry elevated risk of non-replication.

• Regulatory risk. FDA, EMA, MHRA, and other regulatory bodies retain full discretion over approval decisions, labeling, post-marketing requirements, and timelines. Regulatory outcomes can diverge from clinical data interpretation, advisory committee votes, or precedent.

• “Sell-the-news” and post-catalyst volatility. Positive data does not guarantee a positive share price reaction, and negative data does not guarantee a negative one. Pre-event positioning, market expectations, and technical factors can produce outcomes that are disconnected from the underlying clinical or regulatory result.

• M&A speculation. Any commentary on potential mergers, acquisitions, licensing deals, or partnership activity is speculative, based on publicly available information and pattern analysis, and should not be treated as informed by non-public information or as a prediction of any specific transaction, timing, or valuation.

• Forward-looking statements. Any statements regarding probability of success, expected trial timelines, anticipated regulatory pathways, or projected market opportunity are forward-looking, are based on assumptions that may prove incorrect, and are subject to change without notice. Actual outcomes may differ materially.

6. Accuracy, Sourcing, and Third-Party Data

Content is prepared using a combination of public disclosures (SEC/EDGAR filings, company press releases, clinical trial registries), primary scientific literature, and third-party research aggregation tools. While reasonable efforts are made to verify information against primary sources prior to publication, Systima Capital does not warrant the accuracy, completeness, timeliness, or reliability of any data, and specifically disclaims reliance on third-party research platforms, broker commentary, or aggregated data as a primary source of truth. Errors, omissions, or subsequent restatements by primary sources may occur and may not be reflected in previously published Content. Readers should independently verify any material fact before relying on it.

7. Potential Conflicts of Interest

The author, Systima Capital, its principals, affiliates, or contributors may hold, initiate, add to, reduce, or exit positions in securities of companies discussed in the Newsletter, before, during, or after publication, without prior notice. This represents a potential conflict of interest that readers should weigh when evaluating the objectivity of any Content. Where a position is held at the time of publication, reasonable efforts will be made to disclose that fact in-context; the absence of a disclosed position should not be assumed to mean no position exists. Systima Capital does not accept paid promotion, sponsorship, or compensation from any company, security issuer, or related party in exchange for coverage, favorable commentary, or inclusion in the Newsletter.

8. Track Record and Past Performance

Any reference to prior calls, catalyst calls, conviction ratings, or trade directives reflects the author’s analysis at the time of publication and is presented for transparency and educational purposes. Past performance — whether of specific calls, a stated track record, or the Newsletter’s overall analytical framework — is not indicative of, and provides no guarantee of, future results. Hypothetical, backtested, or illustrative return figures do not represent actual trading and are subject to inherent limitations, including the benefit of hindsight.

9. Independent Due Diligence Required

You should not make any investment decision based solely on the Content. Before acting on any information contained in this Newsletter, you should independently research the subject matter, consult primary sources (including but not limited to full clinical trial data, regulatory filings, and company disclosures), and consult with a qualified, licensed financial advisor, and where appropriate a tax or legal professional, who is familiar with your individual financial circumstances, investment objectives, time horizon, and risk tolerance.

10. Risk of Loss

Investing in securities, and in clinical-stage or commercial-stage biotechnology and pharmaceutical companies in particular, involves substantial risk, including the potential for total loss of principal. Volatility in this sector can be extreme and rapid, including around binary catalyst events. No Content should be interpreted as minimizing this risk, and no reader should invest capital they cannot afford to lose.

11. No Solicitation; Jurisdictional Restrictions

This Newsletter is not directed at, and does not constitute an offer or solicitation to buy or sell any security in, any jurisdiction where such offer or solicitation would be unlawful. It is the responsibility of each reader to ensure compliance with the laws and regulations of their own jurisdiction, including any restrictions on the receipt of financial promotions or research content. Content is not tailored to the securities laws of any one country and may not satisfy the disclosure or suitability requirements applicable in your jurisdiction.

12. Third-Party Links and References

The Newsletter may link to or reference third-party websites, research, data providers, or commentary for informational purposes. Inclusion of such references does not constitute an endorsement of that third party’s content, accuracy, or views, and Systima Capital has no control over and accepts no responsibility for third-party content.

13. Limitation of Liability

To the fullest extent permitted by applicable law, Systima Capital, Manos Mastorakis, and any affiliates, contributors, or agents disclaim all liability for any direct, indirect, incidental, consequential, or other loss or damage arising from or in connection with any reliance on the Content, including but not limited to trading losses, lost profits, or lost opportunity, whether such liability arises in contract, tort, or otherwise.

14. Intellectual Property and Redistribution

All Content is the property of Systima Capital unless otherwise attributed and is provided for the personal use of subscribers. Redistribution, reproduction, or commercial use of Content without prior written consent is prohibited.

15. Changes to Content and This Disclaimer

Content may be updated, corrected, or amended after initial publication without retroactive notice. This Disclaimer may be revised from time to time; continued use of the Newsletter following any changes constitutes acceptance of the revised terms.

16. Acknowledgment

By reading, subscribing to, or otherwise engaging with this Newsletter, you acknowledge that you have read and understood this Disclaimer in full and agree that Systima Capital and its principals bear no responsibility for investment decisions made in reliance on the Content.

Stay tuned. Thanks for reading. Systima Capital

Disclaimer at the end of this post

In less than a year, High Risk, High Returns (Biotech Investing Newsletter) has grown to 600+ subscribers - twice having made it to the top 100 fastest-growing finance pages on Substack.

Along the way, we have made friends and met collaborators with whom worthwhile ideas have been exchanged, enriching our content and improving our calls.

Our portfolio has grown 100% with a catalyst prediction success rate of 80%+.

We’re only just beginning.

The vision is to embed portfolio tracking capabilities for users at the different access tiers to help you understand where, how and when we place biotech bets.

A lot of this is completely free, with additional levels of access provided to those who are interested going a step further.

80% of the members have joined in the past 4 months, and 100% of the paid members have joined in the past 3 months.

So, we wanted to make sure new and old joiners have a clear idea of what this Substack newsletter can give you! Also, whether you’re a free subscriber exploring SystimaCapital’s methods, or considering becoming a paid member looking for the full ‘'suite’ - this post is for you.

Quick tip: Bookmark this page on your browser and download the Substack app for full user experience!

Ideas that succeeded and we still believe in (as of 8th August 2026)

• - Post #02: Catalyst Deep Dive: Amylyx Pharmaceuticals (my full clinical & financial take)

• - Post #06: Stock Deep Dive - Rapport Therapeutics (FOMO is big on this one...)

• - Post #10: Akero Therapeutics ($AKRO) acquired by Novo Nordisk ($NOVO)

• Post #13: How to Play The AI-drug discovery theme as a biotech investor (Pt. 1); AI drug discovery primer, key themes & catalysts in the next 12 months

• Post #17: AtaiBeckley ($ATAI): A discussion with the CEO of a Psychedelics Powerhouse - acquired by $LLY

• Post #21: Novartis’ ($NOVN) Lp(a)-targeting pelacarsen (HORIZON) has to be the most anticipated catalyst for 2026 in cardiology

• Bullish!!! No post written, but plenty of due dilligence performed separately. (We entered right after the cancer ‘signals’ drove the stock down in a single day. We are up 100% since then)

• No post written, but plenty of due dilligence performed separately on their ITK inhibitor and broad potential across indications.

• No post written, but plenty of due dilligence performed separately

Investment Approach

Every piece gets a conviction rating and a clear directive; no hedges. If the case is weak, we say pass. If the setup is strong, we say why and what could break it. Sell-the-news risk gets flagged explicitly, because good data and a good stock move are two different things.

We go deep on every catalyst from a scientific, commercial, financial POV and spend time to understand what the market is thinking, where the ‘puck’ is going to move to and we build short and long term conviction, flagging it accordingly for our readers!

Upcoming Features

We plan to make our portfolio selection process more transparent and more actionable for all readers to understand how we prepare, research and action our trades.

Stay tuned!

SystimaCapital

Leave a comment

Next Catalyst Ideas

• Mirum’s HDV readout in H2’26

• Enanta (see STAT6-targeting asset)

• Satellos (DMD data H2’26)

• Kymera (see STAT6 P2b Atopic Dermatitis data YE26)

• …and more

Disclaimer

High Risk High Returns (”HRHR,” “the Newsletter”) is published by Systima Capital. This Disclaimer applies to all Content published on this Substack, on affiliated social channels (including LinkedIn), and in any related communications, unless expressly stated otherwise.

1. General Informational Purpose Only

The Content published in this Newsletter — including articles, catalyst previews, deep dives, post-data reactions, catalyst calendars, charts, commentary, and any related distribution assets — is provided for general informational and educational purposes only. It is intended to help readers understand clinical, regulatory, and competitive dynamics in the biotechnology and pharmaceutical sectors. It is not, and should not be treated as, a substitute for independent research or professional advice.

2. Not Investment, Financial, Legal, or Tax Advice

Nothing in this Newsletter constitutes investment advice, financial advice, trading advice, legal advice, tax advice, or any other form of professional advice. No Content should be construed as a personal recommendation to buy, sell, hold, or otherwise transact in any security, investment product, or asset, including but not limited to the equity, debt, or derivatives of any company discussed. References to specific tickers, companies, catalysts, or trial outcomes are illustrative and analytical in nature, not recommendations of suitability for any individual reader.

3. No Advisor-Client or Fiduciary Relationship

Systima Capital, Manos Mastorakis, and any contributors to the Newsletter are not registered as investment advisers, broker-dealers, or financial planners with the U.S. Securities and Exchange Commission, the UK Financial Conduct Authority, or any other regulatory body, unless explicitly stated. Reading, subscribing to, or engaging with this Newsletter does not create an advisory, fiduciary, or client relationship of any kind. No duty of care is owed to any reader by virtue of their access to the Content.

4. Author Background Is Not a Basis for Reliance

The author holds a PhD in Genetics and an MSc in Finance, and has prior sell-side and buy-side experience. This background informs the analytical framework applied to Content but does not qualify the author to give personalized investment advice, does not constitute a professional certification recognized by any regulator for that purpose, and should not be relied upon as such. Scientific or financial credentials do not eliminate the inherent uncertainty of the subject matter covered.

5. Biotechnology-Specific and Clinical Catalyst Risks

Biotechnology and pharmaceutical investing carries risks that are materially different from, and often greater than, those associated with more established sectors. Readers should understand and independently evaluate the following before making any investment decision:

• Binary outcome risk. Clinical trial readouts, FDA (or other regulatory) decisions, and PDUFA events are binary in nature. Outcomes can result in a total or near-total loss of value in the underlying security, regardless of pre-event analysis, consensus expectations, or historical base rates.

• Clinical trial limitations. Topline, interim, and preliminary data may not reflect final results. Trial design (endpoints, statistical powering, population selection, open-label vs. blinded design) materially affects interpretation. Statistical significance does not guarantee clinical significance, regulatory approval, or commercial success. Small sample sizes and early-phase data carry elevated risk of non-replication.

• Regulatory risk. FDA, EMA, MHRA, and other regulatory bodies retain full discretion over approval decisions, labeling, post-marketing requirements, and timelines. Regulatory outcomes can diverge from clinical data interpretation, advisory committee votes, or precedent.

• “Sell-the-news” and post-catalyst volatility. Positive data does not guarantee a positive share price reaction, and negative data does not guarantee a negative one. Pre-event positioning, market expectations, and technical factors can produce outcomes that are disconnected from the underlying clinical or regulatory result.

• M&A speculation. Any commentary on potential mergers, acquisitions, licensing deals, or partnership activity is speculative, based on publicly available information and pattern analysis, and should not be treated as informed by non-public information or as a prediction of any specific transaction, timing, or valuation.

• Forward-looking statements. Any statements regarding probability of success, expected trial timelines, anticipated regulatory pathways, or projected market opportunity are forward-looking, are based on assumptions that may prove incorrect, and are subject to change without notice. Actual outcomes may differ materially.

6. Accuracy, Sourcing, and Third-Party Data

Content is prepared using a combination of public disclosures (SEC/EDGAR filings, company press releases, clinical trial registries), primary scientific literature, and third-party research aggregation tools. While reasonable efforts are made to verify information against primary sources prior to publication, Systima Capital does not warrant the accuracy, completeness, timeliness, or reliability of any data, and specifically disclaims reliance on third-party research platforms, broker commentary, or aggregated data as a primary source of truth. Errors, omissions, or subsequent restatements by primary sources may occur and may not be reflected in previously published Content. Readers should independently verify any material fact before relying on it.

7. Potential Conflicts of Interest

The author, Systima Capital, its principals, affiliates, or contributors may hold, initiate, add to, reduce, or exit positions in securities of companies discussed in the Newsletter, before, during, or after publication, without prior notice. This represents a potential conflict of interest that readers should weigh when evaluating the objectivity of any Content. Where a position is held at the time of publication, reasonable efforts will be made to disclose that fact in-context; the absence of a disclosed position should not be assumed to mean no position exists. Systima Capital does not accept paid promotion, sponsorship, or compensation from any company, security issuer, or related party in exchange for coverage, favorable commentary, or inclusion in the Newsletter.

8. Track Record and Past Performance

Any reference to prior calls, catalyst calls, conviction ratings, or trade directives reflects the author’s analysis at the time of publication and is presented for transparency and educational purposes. Past performance — whether of specific calls, a stated track record, or the Newsletter’s overall analytical framework — is not indicative of, and provides no guarantee of, future results. Hypothetical, backtested, or illustrative return figures do not represent actual trading and are subject to inherent limitations, including the benefit of hindsight.

9. Independent Due Diligence Required

You should not make any investment decision based solely on the Content. Before acting on any information contained in this Newsletter, you should independently research the subject matter, consult primary sources (including but not limited to full clinical trial data, regulatory filings, and company disclosures), and consult with a qualified, licensed financial advisor, and where appropriate a tax or legal professional, who is familiar with your individual financial circumstances, investment objectives, time horizon, and risk tolerance.

10. Risk of Loss

Investing in securities, and in clinical-stage or commercial-stage biotechnology and pharmaceutical companies in particular, involves substantial risk, including the potential for total loss of principal. Volatility in this sector can be extreme and rapid, including around binary catalyst events. No Content should be interpreted as minimizing this risk, and no reader should invest capital they cannot afford to lose.

11. No Solicitation; Jurisdictional Restrictions

This Newsletter is not directed at, and does not constitute an offer or solicitation to buy or sell any security in, any jurisdiction where such offer or solicitation would be unlawful. It is the responsibility of each reader to ensure compliance with the laws and regulations of their own jurisdiction, including any restrictions on the receipt of financial promotions or research content. Content is not tailored to the securities laws of any one country and may not satisfy the disclosure or suitability requirements applicable in your jurisdiction.

12. Third-Party Links and References

The Newsletter may link to or reference third-party websites, research, data providers, or commentary for informational purposes. Inclusion of such references does not constitute an endorsement of that third party’s content, accuracy, or views, and Systima Capital has no control over and accepts no responsibility for third-party content.

13. Limitation of Liability

To the fullest extent permitted by applicable law, Systima Capital, Manos Mastorakis, and any affiliates, contributors, or agents disclaim all liability for any direct, indirect, incidental, consequential, or other loss or damage arising from or in connection with any reliance on the Content, including but not limited to trading losses, lost profits, or lost opportunity, whether such liability arises in contract, tort, or otherwise.

14. Intellectual Property and Redistribution

All Content is the property of Systima Capital unless otherwise attributed and is provided for the personal use of subscribers. Redistribution, reproduction, or commercial use of Content without prior written consent is prohibited.

15. Changes to Content and This Disclaimer

Content may be updated, corrected, or amended after initial publication without retroactive notice. This Disclaimer may be revised from time to time; continued use of the Newsletter following any changes constitutes acceptance of the revised terms.

16. Acknowledgment

By reading, subscribing to, or otherwise engaging with this Newsletter, you acknowledge that you have read and understood this Disclaimer in full and agree that Systima Capital and its principals bear no responsibility for investment decisions made in reliance on the Content.

Stay tuned. Thanks for reading. Systima Capital

Not just that - but you may have even surpassed your initial calculations of whether 'this’ could work.

I am not saying we are done here; however, what I defined as success one year ago when I was starting - not one - but two newsletters, in two different - somewhat overlapping, but close to my heart topics. These two topics have at their center my passion for health, medicine, science.

In one you look for portfolio gains, in the other you look for health gains.

• High Risk, High Returns (Biotech Investing Newsletter) = HRHR from here onwards

• Young Centenarians (Longevity, Health and Medical Newsletter) = YC from here onwards [more on this on another post - but feel free to explore past posts]

Why HRHR: I left my career as a sellside analyst after half a decade covering pharmaceuticals and biotech companies, going deep into their science, strategy and financials. My favorite part was previewing/predicting clinical catalysts - diving deep into the clinical aspects and preparing for the stock reaction after the readout.

This gave rise to a (by definition) risk-friendly approach to picking stocks - using catalyst calendars as a starting point, picking catalysts that promised significant inflection to the story of a given company and analysing that catalyst through the scientific, commercial, strategic, financial lenses to gain conviction.

Anecdotally, I can say that our calls have been mostly right (80% ongoing success rate).

First of all - a BIG THANK YOU - for supporting, liking, following, pledging, reading, commenting. We do this to help you make better biotech trades and meanwhile enjoy reading about the latest life-changing medicines.

Here are some of the notes you can start with to understand what to expect going forward:

Post #01: Inside the GLP-1 Boom: What a Biotech Analyst (and PhD/Nutritionist) Thinks

• We kicked off with the most popular note - a deep dive on obesity. Lots of hype and attention in this $100bn+ opportunity. We wore our sellside analyst and nutritionist hats to look at this from both perspectives.

Post #02: Catalyst Deep Dive: Amylyx Pharmaceuticals (my full clinical & financial take)

• We picked our first catalyst as a GLP1-adjacent readout (PBH is a disorder where glucose levels fall too low after bariatric surgery - with GLP1 antagonist being explored there). We viewed $AMLX’s readout (still pending) as a no-brainer. The stock has gained since our post and we continue to feel confident about the pending readout later this year.

Post #06: Stock Deep Dive - Rapport Therapeutics (FOMO is big on this one...)

• Our first successful prediction for a stock that is now trading 2x its value prior to our post. We have long term conviction on the name as a potential key player in the space of epilepsy.

Post #9: $ATYR ‘post-mortem’ analysis. What we learned from this and how to position for the next 6-12 months

• Our first unsuccessful prediction. We fell into the FOMO trap and did not trust our instinct on the dangers of having a placebo arm on steroid treatment. We lost some money on this one, but learned a lot through the post-mortem analysis of what went wrong. Such is biotech trading.

Post #10: Akero Therapeutics ($AKRO) acquired by Novo Nordisk ($NOVO)

• Our conviction was there before the write-up had completed. We entered a trade and soon enough saw the same conviction mirrored by $NOVO who acquired in October 2026.

Post #13: How to Play The AI-drug discovery theme as a biotech investor (Pt. 1); AI drug discovery primer, key themes & catalysts in the next 12 months

• Our AI-themed series gained a lot of attention. More importantly, we own two trades that have doubled since the publication highlighting the potential of AI-driven drug discovery.

Post #17: AtaiBeckley ($ATAI): A discussion with the CEO of a Psychedelics Powerhouse

• Another thematic we are bullish on - psychedelics. We spoke to the CEO of and published our thoughts. We have long term conviction on this catalyst-rich set up.

Post #19: Karyopharm’s P3 readout (March 2026) about to shake things up in myelofibrosis. We’re cautious

• We went deep into an important catalyst for the space of myelofibrosis. We said we’re cautious and did not invest; the readout was eventually mixed, stock suffered. It has recovered now, but regulatory success remains unclear and cash runway is a big uncertainty. The stock and the drug may still have potential, but the catalyst was not a win and we called it. We are equally focused on staying out of bad trades as we are on doubling down on good ones.

Post #21: Novartis’ ($NOVN) Lp(a)-targeting pelacarsen (HORIZON) has to be the most anticipated catalyst for 2026 in cardiology

• We love cardiology. We never went so deep into a catalyst as much as we did with this one. Lp(a)-targeted treatment pelacarsen - we think - will transform lipidology (and $NOVN in the process). Bullish on the H2’26 readout. Stay tuned.

Post #24 - $TLSA (na-SPMS) King? A violently binary clinical catalyst resting on solid science

• Our latest post explored - a troubled company with multiple pivots. We expressed our mixed expectations for the catalyst and that we would not be supporting a trade here. Hopefully we are wrong for the sake of multiple sclerosis patients.

That’s it… that’s your starting point if you’ve joined recently and want to see whether to stick around or not! We highly recommend you do.

Share High Risk, High Returns (Biotech Investing Newsletter)

If not - plenty of other great biotech writers out there! Thank you for taking the time to explore our work.

Any feedback is welcome.

PS. The above is not financial advise! Do your own research! Share your thoughts if you wish. Be careful with risk!

Thank you -

Systima Capital

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