Watchlist

Stage / status: Investigational (Phase 2a planning); no off-label or compounding pathway

AlzeCure Pharma (Sweden) lead clinical asset. Novel mechanism — small-molecule pan-Trk allosteric kinase potentiator. Mechanistically distinct from anti-amyloid mAbs and cholinesterase inhibitors — directly relevant given the Cochrane 2026 finding that the entire anti-amyloid class produces only trivial cognitive benef…

Stage / status: Research chem (not FDA-approved; April 22 2026 removed from FDA 503A Category 2 "Do Not Compound" list pending PCAC review before Feb 2027 — removal is NOT approval)

Originally developed at WSU (Harding lab); commercialized via Athira Pharma as fosgonimeton/ATH-1017 — a subcutaneous prodrug rapidly converted to dihexa. Four 2024-2026 events reshape this entry. (1) Sept 2024: Athira's LIFT-AD Phase 2/3 in mild-to-moderate AD missed primary (Global Statistical Test p=0.70) and key se…

Stage / status: Investigational (Phase 3 MASH programs; no FDA-approved product)

Promoted from watchlist because the class now has several named, active Phase 3 MASH programs plus peer-reviewed Phase 2b human data. Efruxifermin HARMONY 96-week results showed sustained histologic MASH/fibrosis signal; pegozafermin ENLIVEN showed NASH/MASH improvements and large triglyceride/liver-fat effects; efimos…

Stage / status: Investigational (pelacarsen Lp(a)HORIZON CVOT readout expected 2026; olpasiran OCEAN(a) Outcomes ongoing)

Until 2025 Lp(a) was a non-modifiable risk factor — the entire class is a major shift. Network meta-analyses (Wu Pharmacol Res 2026; Hu Front Cardiovasc Med 2026) confirm olpasiran most potent. Muvalaplin is uniquely oral and would be the first non-injectable in the class. Concomitant PCSK9i further enhances LDL reduct…

Stage / status: Approved in China (June 2025) for chronic weight management; FDA filing TBD

Innovent Biologics; Chinese-approved for obesity and T2D in 2025. GLORY-1 Phase 3 (China, n>600) showed -16.8% body weight at 32 weeks at 9 mg dose. Meaningful for biohacker readers because it reaches similar magnitude to tirzepatide and is already prescribed in China while Western markets wait. Particular interest for…

Stage / status: Rx (methemoglobinemia, cyanide poisoning, ifosfamide encephalopathy); USP/pharma grade marketed OTC in many jurisdictions as "longevity" supplement — verify pharmaceutical grade only

Hormetic dose-response is the central decision input — biohacker sweet spot is 0.5-2 mg/kg PO. Only USP/pharmaceutical grade is safe orally (industrial/aquarium/photographic grades contain heavy-metal contaminants). Mechanism updated in light of newer literature: MB acts as an alternative electron carrier between NADH …

Stage / status: Investigational (Phase 3)

Jastreboff 2023: ~24% weight loss at 48 weeks in Phase 2 — trajectory suggested continued loss past 48 weeks. TRIUMPH program (Eli Lilly) is a 4-trial basket: TRIUMPH-1 (n=2300, obesity, primary completion April 2026), TRIUMPH-2, TRIUMPH-3 (obesity + CVD), TRIUMPH-4 (OA standalone). Plus TRANSCEND-CKD Ph2b kidney mecha…

Stage / status: Rx (Schedule IV US)

Originally developed by Aerial BioPharma and Jazz Pharmaceuticals; **Axsome Therapeutics acquired Sunosi from Jazz in March 2022** and now drives the development program. Distinguishing pharmacology vs modafinil: direct dopamine + norepinephrine reuptake inhibition (closer to a mild amphetamine than to modafinil); prec…

Stage / status: Investigational (Phase 3)

Boehringer Ingelheim/Zealand Pharma. SYNCHRONIZE-1 (no T2D, n=725) and SYNCHRONIZE-2 (with T2D, n=752) Phase 3 trials enrolling — both 76-week trials with primary endpoint % body weight change. Phase 2 (Le Roux 2024 Lancet) showed up to 19% weight loss. Particular promise for metabolic-associated steatotic liver diseas…

Stage / status: Investigational

Heymsfield JAMA 2021: -20.5% fat mass with +3.6% lean mass gain at 48 weeks. Unique profile: most weight-loss drugs (incl. GLP-1s) cost ~25-30% of weight loss as lean mass. Now owned by Lilly — actively being explored as combo with tirzepatide for body recomposition. Highlighted in 2026 obesity-pharmacotherapy reviews …

Stage / status: Investigational; CagriSema combination filed for approval 2025

REDEFINE 1 (Garvey NEJM 2025): CagriSema 2.4mg/2.4mg achieved -20.4% body weight at 68 weeks vs -3.0% placebo (n=3417, no T2D). Notably below the ~25% projected from Phase 2 — Novo stock fell at the December 2024 readout. Cagrilintide alone -11.5%. REDEFINE 2 (T2D, n=1206): -13.7% vs -3.4% placebo at 68 weeks. REDEFINE…

Stage / status: Investigational / compounded (Androxal was not FDA-approved; no FDA-approved US product)

Cleaner pharmacology than mixed clomiphene because it lacks zuclomiphene, the longer-lived estrogenic isomer. Phase 2/3 studies showed testosterone restoration while maintaining sperm counts, unlike testosterone gel. FDA did not approve Androxal after the 2015 review cycle, so US access is compounded or research-market…

Stage / status: Research chem; formerly investigational drug

Developed by Nippon Shinyaku; acquired by Aevi Medical then Supernus. Phase 2 in adolescents with ADHD and mGluR network mutations showed modest effect; Phase 3 program effectively halted. Popular in nootropic circles; limited tolerance.

Stage / status: Investigational (Phase 3)

Amgen. Phase 2 (Jastreboff NEJM 2025, n=592, NCT05669599): obesity cohort -12.3% to -16.2% body weight at 52 weeks vs -2.5% placebo; T2D cohort -8.4% to -12.3% with HbA1c -1.2 to -1.6 percentage points. Once-monthly dosing is the differentiator vs weekly GLP-1s. Counterintuitive that BOTH GIP agonism (tirzepatide) AND …

Stage / status: Investigational/Rx biologics depending program; WADA S4 prohibited

WADA coverage: activin A-neutralizing antibodies, activin receptor IIB competitors, decoy activin receptors, ACE-031, anti-activin receptor IIB antibodies, myostatin inhibitors, agents reducing or ablating myostatin expression, myostatin-binding proteins, follistatin, myostatin propeptide, myostatin- or precursor-neutr…

Stage / status: Research chem (was investigational drug)

Ph2 MDD trial (Fava 2016) missed primary endpoint despite promising Ph1b. Neuralstem (now Palisade Bio) largely discontinued development. Sold as research chemical. Claims of hippocampal volume restoration in depression preclinical models.

Stage / status: Investigational (NewAmsterdam Pharma; FDA filing expected 2025-2026; PREVAIL CVOT readout expected 2026-2027)

Revival of CETP inhibition after the torcetrapib (BP/mortality) and dalcetrapib (futile) failures. Obicetrapib's hydrophilic structure avoids torcetrapib's off-target effects. BROADWAY trial: -32% LDL on top of max statin. Triple combo (obicetrapib + ezetimibe + statin) ranks highest in 2026 network meta for LDL/ApoB r…

Stage / status: Investigational/not approved for performance; WADA S0 prohibited

WADA coverage: ryanodine receptor-1-calstabin complex stabilizers, S-107, S48168/ARM210, troponin activators, reldesemtiv and tirasemtiv. Included as perceived muscle-performance enhancers, not established healthspan tools.

Stage / status: Investigational (Stealth BioTherapeutics)

Specifically targets dysfunctional mitochondria — novel MOA. Promising data in primary mitochondrial myopathy and heart failure with preserved EF. Not yet FDA approved. Represents emerging mitochondria-targeted therapeutic class.

Stage / status: Investigational in multiple jurisdictions; not approved

Saniona now developing for hypothalamic obesity (rare disease orphan indication). Substantial weight loss in obesity trials. Cognitive trials disappointed. Research chem availability exists; caution with CV effects.

Stage / status: Phase 1/2 · Novo Nordisk

Unimolecular GLP-1 / amylin co-agonist in both oral and SC formats. If the early Phase 1 weight-loss signal (~13% in 12 weeks oral, ~24% in 36 weeks SC) holds through Phase 2, it would be the first single-molecule approach matching tirzepatide-class effect sizes with the oral-route advantage.

Next milestone: Phase 2 readout expected 2026 H2 - 2027 H1

Stage / status: Phase 2 · Eli Lilly

Long-acting amylin analog being developed as monotherapy and as a stack partner for tirzepatide. Amylin alone has been a long-time mechanistic story (pramlintide) without a long-acting product; eloralintide would be the first.

Next milestone: Phase 2 dose-ranging data 2026-2027

Stage / status: Phase 3 (China-approved; West pending) · Innovent / Eli Lilly

GLP-1 / glucagon dual agonist already approved in China (June 2025) on GLORY-1 showing -16.8% at 32 weeks. Western Phase 3 data and FDA filing are the next decision-relevant events. Stronger hepatic-fat-oxidation signal than pure-GLP-1 agents — particularly interesting for MASLD comorbidity.

Next milestone: Western Phase 3 readouts and FDA filing 2026-2027

Stage / status: Phase 3 · Ionis (olezarsen) / Arrowhead (plozasiran)

ApoC-III inhibitors for severe hypertriglyceridemia and FCS (familial chylomicronemia syndrome). Olezarsen FDA-approved for FCS Dec 2024. Watch for indication expansion to severe HTG and cardiovascular outcomes — would broaden into the >500 mg/dL TG population currently served by icosapent ethyl and fenofibrate.

Next milestone: Olezarsen severe HTG indication expansion 2026; plozasiran SHASTA Phase 3 readouts

Stage / status: Approved (HoFH); broader indications pending · Regeneron (evinacumab) / Arrowhead (zodasiran)

ANGPTL3 inhibition lowers LDL, TG, and HDL via a separate pathway from PCSK9. Currently approved only for homozygous FH; broader Phase 3 work in refractory dyslipidemia and severe HTG is the question. RNA-targeted zodasiran would lower the cost of chronic administration vs the antibody form.

Next milestone: Broader-indication Phase 3 outcomes 2026-2028

Stage / status: Phase 3 (menopause); approved as contraceptive · Mithra / Estetra

Native fetal estrogen with selective ER activation profile and apparently cleaner thrombotic risk than synthetic estrogens. Already approved as the contraceptive Donesta/Estelle. Menopause indication would offer an alternative for women with HRT contraindications (clot risk, family history) without the non-hormonal compromise of NK3 antagonists.

Next milestone: Menopause Phase 3 readout 2026-2027

Stage / status: Phase 3 (China; AGA) · Kintor Pharmaceutical

Topical androgen receptor antagonist for androgenetic alopecia. Mechanism allows scalp-targeted DHT blockade without the systemic sexual side-effect profile of oral finasteride/dutasteride. China Phase 3 ongoing; US Phase 2 mixed but Phase 3 design improvements may rescue.

Next milestone: China Phase 3 readout and US Phase 3 design 2026

Stage / status: Phase 2 (AGA); approved for acne · Cassiopea / Sun Pharma

Topical androgen-receptor antagonist already FDA-approved 2020 for acne. Hair-growth Phase 2 data exist; Phase 3 for AGA would broaden access to a non-systemic anti-androgen for AGA — complementary or competitive with pyrilutamide.

Next milestone: AGA Phase 3 program initiation 2026

Stage / status: Approved (schizophrenia, bipolar dep monotherapy); MDD adjunct Phase 3 · Intra-Cellular Therapies (J&J)

Atypical antipsychotic with serotonin, dopamine, and glutamatergic mechanism; clean metabolic profile. Already approved for bipolar depression. MDD adjunct Phase 3 program is the next expansion — would put a non-SSRI, non-SNRI option into the adjunctive-MDD space dominated by atypicals.

Next milestone: MDD adjunct Phase 3 readouts 2026

Stage / status: Approved (schizophrenia, bipolar) · Alkermes

Olanzapine plus an opioid antagonist designed to blunt olanzapine's notorious weight gain. Real-world data on whether the metabolic-mitigation signal from registration trials holds at population scale.

Next milestone: Real-world metabolic-outcome data 2026-2027

Stage / status: Phase 3 (Pelage Pharma); compounded availability · Pelage Pharma / Hims

Reformulated topical finasteride targeting scalp DHT reduction without systemic sexual side effects (the central concern with oral finasteride). Compounded versions already available; standardized FDA-approved version would change the AGA market substantially.

Next milestone: Phase 3 readout 2026-2027

Stage / status: Phase 1 (first-in-human) · Verve Therapeutics

First-in-human CRISPR base-editing of PCSK9 in liver — one-time injection producing durable LDL reduction. If long-term follow-up confirms safety and durability, it reframes the entire LDL-lowering market away from chronic dosing. Distinct from siRNA-PCSK9 (inclisiran) which still requires periodic dosing.

Next milestone: Phase 1b long-term follow-up + Phase 2 design 2026-2027

Stage / status: Investigator-initiated · Multiple (Eisai/Lilly)

Both anti-amyloid mAbs are approved as monotherapies. Sequential or combination use would target different amyloid species (lecanemab → protofibrils; donanemab → plaques) but ARIA-E risk compounds. Cochrane 2026 already found trivial cognitive benefit for the monotherapy class — combinations would need to either dramatically improve efficacy or dramatically reduce ARIA to be worth it.

Next milestone: Investigator-initiated trial designs 2026-2027

Stage / status: Available now; emerging consensus · Multiple labs

Beyond standard ApoB and Lp(a) — next-generation CV risk markers that complement the lipid panel. Lp-PLA2 (inflammation in artery wall), oxLDL (atherogenic lipid oxidation), fibrinogen (clotting risk). Increasingly available via consumer labs but lacking large-cohort validation comparable to ApoB.

Next milestone: Consumer-lab integration and validation studies ongoing

Stage / status: Available now; consumer · Multiple

Next-generation aging biomarkers beyond methylation-based epigenetic clocks. iAge measures immune-inflammation status; GlycanAge measures IgG glycosylation; DunedinPACE measures rate of aging rather than biological age. Watch for which proves most actionable — sensitivity to intervention vs static prediction.

Next milestone: Intervention-sensitivity validation studies 2026-2028

Stage / status: Research chem (not FDA-approved; April 22 2026 removed from FDA 503A Category 2 "Do Not Compound" list pending PCAC review before Feb 2027 — removal is NOT approval)

Originally developed at WSU (Harding lab); commercialized via Athira Pharma as fosgonimeton/ATH-1017 — a subcutaneous prodrug rapidly converted to dihexa. Four 2024-2026 events reshape this entry. (1) Sept 2024: Athira's LIFT-AD Phase 2/3 in mild-to-moderate AD missed primary (Global Statistical Test p=0.70) and key se…

Stage / status: Approved in China and Italy for cholestatic disease; was an active ingredient (as taurursodiol) in FDA-approved Relyvrio/AMX0035 for ALS — withdrawn after PHOENIX Phase 3 failure; sold OTC in US as dietary supplement (gray area)

Tauroursodeoxycholic acid is the taurine conjugate of UDCA — more hydrophilic and slightly more cytoprotective than UDCA itself. **Clinical anchors**: Ma 2016 (Medicine) n=199 China PBC trial — TUDCA non-inferior to UDCA at 500-1500 mg/day with possible superior pruritus relief; Kars 2010 (Diabetes) 1750 mg/day x 4 wk …

Stage / status: FDA-cleared (Mar 2024) · Dexcom

First FDA-cleared OTC continuous glucose monitor for non-diabetics — fundamentally changes biohacker access to glucose data without prescription gatekeeping. Already on market; the question is how the data shapes biohacker dietary discourse over the next 1-2 years.

Next milestone: Real-world adoption + Levels/Nutrisense competitive landscape 2026