Relay Therapeutics: It Could Be Time To ‘Be Greedy When Others Are Fearful’ (NASDAQ:RLAY)

Funding Overview – Money Intensive However Money Wealthy – At Present Value Relay Affords The Affected person Investor Worth

I’ve lined Relay Therapeutics (NASDAQ:RLAY) a number of occasions for In search of Alpha because the firm accomplished what was, at the time, the third largest biotech IPO in historical past, elevating ~$400m at a worth of $20 per share in July 2020.

Relay already had raised $520m from a personal funding spherical that included contributors such because the SoftBank Imaginative and prescient Fund, Google Ventures, the Biotechnology Worth Fund, and Third Rock Ventures, giving it a battle chest of >$1bn.

In its Q322 10Q submission Relay describes itself as follows:

We’re a clinical-stage precision drugs firm reworking the drug discovery course of by combining modern computational and experimental applied sciences with the purpose of bringing life-changing therapies to sufferers.

As we consider we’re among the many first of a brand new breed of biotech created on the intersection of disparate applied sciences, we goal to push the boundaries of what is potential in drug discovery.

One concern with this new breed of drug discovery firms is that their leading edge know-how platforms are usually capital intensive. As of Q322, Relay’s whole working bills for the 12 months had been $228m, in comparison with $299m within the prior 12 months interval, and web loss was $223m, versus $296m within the prior 12 months interval.

In equity, Relay has been in a position to full extra on the market fundraisings of ~$350m in October 2021, and $300m in September 2022, that means as of Q322, Relay reported a money place of $1.1bn. That can be enough to fund operations till 2025, administration says.

The fundraisings – and the biotech bear market of 2022, which noticed traders pull cash out of the biotech sector, looking for safer havens that supplied nearer time period industrial income alternatives, have dragged Relay’s share worth down from a post-IPO worth of >$50, to a worth as little as $14 as of December final 12 months.

At right this moment’s share worth of $17.5, Relay nonetheless boasts a market cap valuation >$2bn, which is excessive for a drug developer that has not progressed any asset past Section 1 medical research, but additionally probably engaging – given the rewards on provide – for traders ready to be affected person.

Pipeline Focus – FGFR2 Inhibitor Affords Approval Shot, Label Expansions, Validation of Method

As we will see above Relay’s excessive money spend has allowed the corporate to develop a promising pipeline of belongings utilizing its Dynamo platform, which the corporate says:

Integrates an array of modern computational and experimental approaches designed to drug protein targets which have beforehand been intractable.

Close to time period, Relay’s industrial alternatives are small scale. Its most superior asset so far is RLY-4008, an oral small molecule inhibitor of fibroblast progress issue receptor 2 (“FGFR2”), which is predicted to enter a pivotal research this 12 months in sufferers with Cholangiocarcinoma (“CCA”), in any other case generally known as bile duct most cancers – expressing FGFR2 mutations.

CCA has a affected person inhabitants of ~1,000 within the US, Relay estimates, and due to this fact represents a income alternative that is seemingly <$100m every year. Extra encouraging, nevertheless, is the potential for increasing the drug into new indications.

The FDA has authorised three FGFRs lately:

• Incyte’s (INCY) Pemazyre (pemigatinib) was authorised in April 2020 in unresectable regionally superior or metastatic CCA exhibiting FGFR2 fusion, incomes $83.5, of revenues in FY22.
• Privately-owned Taiho Oncology’s Lytgobi (futibatinib) was authorised in October final 12 months for remedy of intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions.
• Janssen Prescription drugs’ Balversa (erdafitinib) was authorised in April 2019 for remedy of sufferers with regionally superior or metastatic urothelial (bladder) most cancers. Gross sales haven’t been disclosed by Johnson & Johnson (JNJ), Janssen’s father or mother firm, though JNJ apparently believes the drug can attain blockbuster (>$1bn every year) gross sales primarily based on label growth alternatives.

Relay believes one thing much like Janssen within the case of RLY-4008. Utilizing its increased decision know-how, Relay was in a position to determine that concentrating on FGFR2 versus FGFR1 – as Pemazyre, Lytgobi, and Balversa do – offers its candidate superior selectivity, goal inhibition and tolerability – and Relay has produced the info to show this thesis.

As we will see above the three authorised FGFR concentrating on medicine have been in a position to generate a mean 36%-42% Goal Response Charge (“ORR”) in medical research in CCA. Interim information from Relay’s Section 1 ReFocus research nevertheless has proven an ORR of 88% (15 of 17 sufferers) on the dose stage – 70mg QD – it’s going to use in its pivotal research of the drug in CCA. Throughout all doses, the ORR achieved was 63% (24 of 38 sufferers).

Admittedly, RLY-4008 has not been in a position to generate any full responses (“CRs”) to this point – solely partial responses (“PRs”), however on the time of the info cutoff, 13 of 15 excessive dose responders remained in remedy and as importantly, Relay reported from a security perspective that:

Most AEs have been anticipated FGFR2-on goal, low-grade, monitorable, manageable and largely reversible

As above, Relay is now within the strategy of initiating a pivotal fusion optimistic CCA growth cohort that might probably pave the best way for an accelerated approval of RLY-4008 in CCA, maybe as early as 2024 given the cohort is predicted to be totally enrolled by the tip of the 12 months.

And simply as importantly – for traders in search of greater than a <$100m income alternative – Relay additionally will provoke a non-CCA cohort trying on the capability of RLY-4008 to focus on different kinds of strong tumor.

The truth that RLY-4008 can goal FGFR mutations and amplifications in addition to fusion probably will increase the candidates’ addressable market in comparison with its rivals, and as we will see in the course of the above slide from Relay’s newest investor presentation, FGFR alterations are noticed throughout a number of tumor sorts, together with pancreatic, pores and skin / melanoma, lung and breast most cancers – markets that add as much as an addressable market that simply exceeds $50bn.

To summarize, having spent seemingly >$600m in 2021 and 2022, traders have a proper to demand tangible indicators of progress, and Relay has broadly delivered that progress.

That is to not recommend that RLY-4008 is a slam dunk that is assured to validate Relay’s strategy with a CCA approval, after which make the corporate worthwhile by commanding blockbuster gross sales, however neither is it an excessive amount of of a stretch to consider which may be the case.

Establishing A Breast Most cancers Franchise

Clearly Relay’s alternatives stretch past its FGFR inhibitor candidate, even when that is essentially the most outstanding near-term industrial alternative.

In breast most cancers, Relay has bold plans to ascertain a drug franchise and its strategy / thesis is much like the FGFR alternative. With its superior modeling instruments, Relay has been in a position to create what it believes are the primary full size buildings of a pan-mutant and isoform-selective phosphoinostide 3 kinase alpha, or PI3Ka for brief.

In doing so, Relay has been in a position to determine a “novel allosteric pocket” to focus on – versus the “orthosteric,” extra simply accessible however probably much less promising websites that conventional drug discovery approaches have targeted upon. Relay’s candidate is called RLY-2608.

As soon as once more – though this time primarily based on preclinical research solely – Relay believes that its PI3KA has superior properties to e.g. Danish pharma large Novartis’ Piqray (alpelisib), which earned ~$370m of revenues in FY21, or Roche’s (OTCQX:RHHBY) Section 3 stage candidate Inavolisib, additionally indicated for breast most cancers.

RLY-2608 will shortly develop into the primary mutant (versus wild sort) selective inhibitor to enter the clinic, backed by encouraging preclinical information as proven under.

One arm of the research will deal with RLY-2608 plus fulvestrant – a sort of hormone remedy – in sufferers with PIK3CA mutated breast most cancers, whereas the opposite will have a look at different strong tumors that specific PIK3CA corresponding to ovarian, cervical and head and neck cancers. Each arms of the research will then enter a dose growth part with 15 sufferers in every indication.

The preliminary medical information replace has been promised for the primary half of this 12 months, which is probably sturdy upside catalyst for traders to look ahead to (though disappointing outcomes will conversely drag the share worth down).

The plan is to then introduce two different members of its PI3KA franchise into the combination: RLY5836 – which has a “comparable medical profile, however totally different chemical properties” to RLY-2608, in line with Relay, adopted by an “H1047R-specific” candidate – H1047R being a “hotspot” mutation that is discovered inside the kinase area of PI3KA.

And that is not all – subsequent will come a selective Cyclin-dependent kinase 2 (“CDK2”) asset – CDK2 being a gene encoding a protein related to most cancers cell proliferation – adopted by an Estrogen Receptor (“ERα”) degrader – protein degradation being an thrilling however unproven methodology of dipsosing of undesirable proteins inside a cell.

At this early stage within the growth cycle it is most likely pure for any potential investor in Relay to harbor doubts as as to whether all of those new asset sorts will add as much as greater than the sum of their elements, and genuinely be capable to ship a industrial stage breast most cancers franchise.

The breast most cancers market is predicted to succeed in ~$70bn in measurement by 2030, and is usually the area of huge pharmas corresponding to Gilead Sciences (GILD), Roche, Johnson & Johnson, Pfizer (PFE) and many others., which is not going to wish to loosen their grip on the area.

With that mentioned, Relay’s strategy has a specific amount of preclinical validation to it, and the corporate is delivering on its promise – particularly to create extra refined modeling of oncogenic drivers and mutations and determine methods of concentrating on them extra successfully.

I’d not be overly stunned if Relay’s Dynamo engine offers the corporate a slight edge over even a big Pharma concern. In the event you additionally end up persuaded by Relay’s progress so far, then investing right this moment, when the corporate is price a fraction of what it was post-IPO, seems like a smart transfer.

Relay is buying and selling at simply 2x money, in spite of everything, and we might see it commercialise a primary asset inside two years, which for my part, marks it out as some of the promising and outstanding precision oncology firms, with an affordable probability of constructing – from the bottom up – a genuinely progressive one-stop-shop for breast most cancers remedy.

If such a state of affairs had been to come up, traders can relaxation assured that Relay’s share worth is assured to rise by not less than 2/3 occasions.

Genentech Collaboration An Further Fillip

One concern or query traders could run alongside the traces of “if Relay’s platform is so spectacular, why is Large Pharma not queueing as much as accomplice with its know-how?”

In Relay’s case, nevertheless, it does have an ongoing partnership with Genentech, which is Roche’s drug growth subsidiary, over an inhibitor of Src homology area 2 domain-containing phosphatase-2, or SHP2 identify RLY-1971. This candidate entered a Section 1 research in 2020, and in line with Relay’s Q322 10Q submission:

Genentech initiated the cohort of RLY-1971 together with GDC-6036, its KRAS G12C inhibitor, in a Section 1b trial in July 2021, and a Section 1b trial of RLY-1971 together with atezolizumab in August 2022.

KRAS is an thrilling druggable goal that’s focused by two recently-approved, medicine, Amgen’s (AMGN) Lumakras and Mirati Therapeutics (MRTX) Krazati. Each are anticipated to ship blockbuster gross sales, though a subsequent era candidate might enhance on each medicine security and efficacy profiles, and maybe develop past later line lung most cancers. Atezolizumab is Roche’s reply to Merck’s >$20bn promoting most cancers surprise drug Keytruda – an immune checkpoint inhibitor that usually works higher when paired with an adjuvant remedy.

Genetech Relay has acquired a $75m upfront fee and there is an choice to enter right into a revenue / value sharing settlement, or to obtain as much as $685m in milestone funds, plus royalties on web gross sales. A helpful extra income, whereas the partnership raises a potential M&A chance that may seemingly happen at a considerable premium to Relay’s present valuation.

Relay could not have secured as many or as excessive worth offers with huge pharma as some drug builders have – to call a pair, Arrowhead (ARWR) and Poseida Therapeutics (PSTX) – however arguably Relay doesn’t must, because it has >$1bn money and maybe prefers to not sacrifice future revenues for the close to time period money injections such partnerships present.

Conclusion – I Like Relay’s Outlook Since I Really feel I Know What I am Investing In

An previous funding adage runs that you must by no means put money into what you do not perceive, and due to this fact it could sound silly of me to say that I consider in Relay’s know-how and strategy. Since I am not a biophysicist or biochemist, how can I make sure I’m not having the wool pulled over my eyes?

To reply that, firstly I truly discover that Relay’s displays and investor communications are telling me a narrative that makes a specific amount of sense. Even when I do not perceive exactly how e.g. the compound mapping works, having adopted Relay for a number of years the consistency of strategy – and of messaging – impresses me.

From the outset Relay has been clear about the way it will use its drug discovery engine and what it is in search of. The institution of such a promising pipeline in such a brief area of time validates the strategy, for my part.

Outlining a whole strategy to constructing a breast most cancers franchise to a layman can’t be a straightforward activity, however I personally discover every drug sort recognized and the outline of how it will likely be utilized in a medical trial each acquainted in that I am conscious medicine with these mechanisms of motion are in excessive demand, and progressive, in that it is sensible how they could be used collectively.

Secondly, it could solely be a small market, however Relay has a real shot at a drug approval inside the subsequent two years. If you have a look at what rival builders have completed in the identical FGFR area, it is laborious to not be impressed by Relay’s information, and there is seemingly a bona fide alternative in play to develop the label of RLY-4008 quickly upon a primary approval.

Thirdly, a smart investor as soon as suggested that I ought to “be grasping when others are fearful.” Hedge funds and enterprise capital largely turned its again on Relay in 2022, however for many who are ready to be extra affected person than establishments which have prospects to impress with short-term yields and upside, Relay inventory seems low cost right this moment, for my part.

$2.1bn remains to be a considerable valuation for a pre-commercial firm that’s not less than 18 months away from a primary full approval in a small market, but when that continues to be the best way the market thinks about Relay, I would be broadly blissful to make the guess that they underestimate this firm, its know-how, and its pipeline.