I can sit through a biotech presentation and come away convinced that the company has discovered the answer to half the problems in modern medicine.

The slides look terrific. The market opportunity is enormous. Management seems pretty sure the rest of us will eventually recognize its brilliance.

Then I look at who is buying the stock.

That is usually where things get more interesting.

An executive spending a million dollars of personal money gives me considerably more to work with than another presentation about shareholder value.

We have some of that buying in Xenon Pharmaceuticals (XENE), Relmada Therapeutics (RLMD), NeOnc Technologies Holdings (NTHI), and MAIA Biotechnology (MAIA).

The purchases include CEOs and CFOs. At NeOnc, the doctor helping develop the drugs has been buying alongside the CEO.

These companies are trying to treat epilepsy, bladder cancer, brain cancer, and lung cancer.

If their drugs work and make it through the approval process, the businesses could become much more valuable. Investors can benefit well before approval if convincing results cause the market to take those possibilities more seriously.

Clinical biotech requires a different approach from buying an established business at a discount.

The price matters, but so do the trial evidence and the money available to finish development.

We need to consider what happens if the next study disappoints or takes longer than expected.

I want a position that can reward us handsomely without letting one bad result wreck the portfolio.

Xenon Pharmaceuticals (XENE): Executives Buy After a Setback

On Sept. 30, CEO Ian Mortimer bought 30,000 shares at $37.38, putting approximately $1.12 million into Xenon.

CFO Thomas Patrick Kelly purchased another 15,000 shares at about $37.32 for roughly $560,000.

Between them, they spent about $1.68 million.

I pay particular attention when the CFO buys.

That person knows how much cash the company has, how quickly it is spending it, and what the next round of development is likely to cost.

Substantial purchases by both executives earn a closer look.

Xenon’s main drug is azetukalner. It opens Kv7 potassium channels to help calm excessive electrical activity in nerve cells.

Epilepsy is its most advanced application, and on Sept. 17, the company announced that it had submitted its FDA application for focal seizures.

Positive Phase 2b and Phase 3 results support the submission.

Focal seizures start in one part of the brain.

For patients who continue having seizures despite existing medicines, another effective treatment could make a considerable difference.

Xenon is also studying azetukalner in primary generalized tonic-clonic seizures, which could eventually expand its use.

The same drug is being studied for major depressive disorder and bipolar depression.

That part of the story recently hit a problem.

Xenon voluntarily paused enrollment of new patients in its psychiatric studies after reviewing neuropsychiatric adverse events.

Patients already enrolled continued in the studies, and the epilepsy program continued.

Results from the X-NOVA2 depression trial are expected in the first quarter of 2027.

We have to take that seriously.

A safety problem does not disappear because the CEO buys shares.

The timing does tell us that the executives were willing to commit substantial money after the setback became public.

For me, the investment case begins with epilepsy.

Approval followed by a successful launch would give Xenon its first commercial product.

That is a big change for a business that has been spending money to develop medicines.

The depression opportunity could add substantially to the value, but it needs favorable results and an acceptable safety profile.

I would be careful about paying much for that possibility until we learn more.

Xenon has other drugs coming along, too.

XEN1701 and XEN1720 target Nav1.7 sodium channels, while XEN1120 targets Kv7 channels. These early clinical programs are aimed at pain.

There is also an earlier program for Dravet syndrome and an epilepsy candidate being developed with Neurocrine Biosciences.

The balance sheet gives Xenon some room to work.

At June 30, it had approximately $1.25 billion in cash and marketable securities, with management projecting enough funding into 2029.

That money supports development and preparations for a possible launch.

It also makes a delay easier to absorb.

Relmada Therapeutics (RLMD): A $1.67 Million Bet on Bladder Cancer

Relmada’s two senior executives have made substantial purchases as the company prepares to advance its lead bladder cancer treatment.

CEO Sergio Traversa bought 200,000 shares over Sept. 9 and 10 for approximately $828,000.

CFO Maged Shenouda bought another 200,000 shares during the same two days for approximately $844,000.

Their combined investment was about $1.67 million.

Relmada’s lead program, NDV-01, combines gemcitabine and docetaxel in a formulation delivered directly into the bladder.

It is being developed for non-muscle invasive bladder cancer, where the disease has not invaded the bladder’s muscle layer.

The formulation is designed to keep the drugs in the bladder and release them gradually over about 10 days.

The goal is better local exposure in a treatment that a urologist can administer conveniently in the office.

You can see why that would matter.

Patients with recurring bladder cancer can face repeated procedures and, in difficult cases, the prospect of losing their bladder.

A treatment that helps control the disease and preserve the bladder would be worth having.

The early results are encouraging.

Relmada reported a 76% complete response rate at 12 months, or 19 of 25 patients assessed at that point.

Among patients whose disease was unresponsive to BCG, an established treatment, eight of 10 had a complete response at 12 months.

Those numbers deserve attention, along with their small denominators.

This was a single-arm study, and we need further evidence before treating the results as settled.

The FDA has provided supportive feedback on two possible paths toward registration.

One addresses difficult BCG-unresponsive disease with carcinoma in situ.

The other addresses intermediate-risk disease after tumor removal.

Success could give NDV-01 more than one opportunity in bladder cancer.

Before that happens, Relmada has to get manufacturing sorted out.

Its August update pushed the expected investigational application to year-end 2026, with the Phase 3 RESCUE program to begin after clearance.

The earlier timetable had slipped.

That is the next thing I want to see: trial material ready, the application cleared, and patients entering the studies.

An encouraging drug still needs to be manufactured reliably.

There is a second program, sepranolone, which modulates signaling associated with GABA receptors.

Relmada plans to study it in Prader-Willi syndrome, a rare genetic disorder with serious behavioral and developmental complications.

Tourette syndrome and obsessive-compulsive disorder are also conditions identified in the drug’s development rationale.

Relmada reported $217.7 million in cash, equivalents, and short-term investments at June 30.

Management expects that to carry the company through 2029, including completion of the NDV-01 Phase 3 program.

Relmada has money to pursue a treatment with promising early results, and its two senior executives have made substantial purchases before the manufacturing and clinical questions are answered.

If the company gets the studies underway and the results hold up, the market would have a much stronger reason to value NDV-01 as a future commercial product.

NeOnc Technologies Holdings (NTHI): Insiders Back a Brain Cancer Breakthrough Attempt

The blood-brain barrier protects the brain, but it also makes treating brain cancer more difficult.

NeOnc is working on two programs intended to address that problem: NEO100, administered through the nose, and NEO212, taken orally.

NEO100 is purified perillyl alcohol.

Its recent Phase 2a study involved patients with recurrent or progressive high-grade gliomas carrying an IDH1 mutation.

NeOnc reported that six-month progression-free survival was 48.9%, compared with a prespecified historical benchmark of 20%.

Median overall survival was approximately 26 months.

I understand why those results generated interest.

I also want readers to understand their limits.

There were only 24 patients and no randomized control group.

The company disclosed that the highlighted analysis used updated response criteria and an estimation method different from the protocol-specified approach.

We need confirmation in larger studies.

The people running NeOnc have been buying since the August results.

Through its Sept. 16 update, CEO Amir Heshmatpour had purchased 111,000 shares for approximately $418,700.

Founder Thomas Chen, the chief medical officer and chief scientific officer, had purchased 49,016 shares for approximately $210,000.

That is about $629,000 of personal money invested in the open market.

The doctor’s participation is particularly interesting to me because he is directly involved in the development effort.

NEO212 combines temozolomide, an established chemotherapy drug, with NEO100 in an investigational oral molecule.

The company is studying it for central nervous system cancers, including recurrent glioblastoma.

Phase 1 dose escalation is complete, and a Phase 2 dose has been selected.

An FDA meeting is scheduled for Nov. 17 to discuss the next steps.

The useful information will be what the agency says about the development plan and the evidence NeOnc will need.

If larger studies confirm meaningful benefits and the company secures a feasible path toward registration, these programs could become considerably more valuable.

A development partner could also become interested as the evidence improves.

Funding will matter throughout.

NeOnc raised $15 million in a September offering that included warrants.

As investors, we have to watch how much new stock is issued along the way.

A drug can become more valuable while dilution absorbs part of the gain that existing shareholders hoped to receive.

MAIA Biotechnology (MAIA): Targeting Cancer at the Chromosome Level

MAIA is trying to turn cancer’s own machinery against it.

Its lead drug is ateganosine, also called THIO.

It targets telomeres, the protective ends of chromosomes.

Many cancer cells use an enzyme called telomerase to maintain those structures.

Ateganosine is designed to exploit that process, damage the telomeres, and help provoke an immune response against the cancer.

The main clinical effort is in non-small cell lung cancer after patients have progressed on earlier treatments.

MAIA gives ateganosine first, followed by cemiplimab, an immune checkpoint inhibitor.

Its Phase 3 trial, THIO-104, compares that sequence with the investigator’s choice of treatment in third-line disease.

That comparison should provide better evidence about whether the approach improves outcomes.

In the Phase 2 expansion, MAIA reported disease control in 19 of 21 evaluable patients, or 90.5%.

Disease control includes stable disease as well as tumor responses.

It is encouraging, and the Phase 3 results will help us judge how much confidence to place in it.

Director Ramiro Guerrero has been buying repeatedly.

Between Aug. 20 and Sept. 10, he acquired 185,078 shares for approximately $252,284.

Founder and CEO Vlad Vitoc added 73,000 shares on Sept. 14 at $1.37, spending about $100,000.

Together, they committed roughly $352,000.

Repeated purchases over several weeks give me more reason to investigate than an isolated token purchase.

MAIA is also exploring other cancer indications and developing a second generation of telomere-targeting compounds.

Those efforts are much earlier, but they could provide additional opportunities if the approach proves useful.

The immediate investment case rests on lung cancer.

Favorable results from the pivotal trial could substantially increase the value of ateganosine and put MAIA in a better position to negotiate financing or a partnership.

Evidence of benefits in other cancers would give us more to work with later.

The company raised approximately $33 million gross in March.

Management said the net proceeds were expected to fund the ongoing pivotal trial.

That supports the immediate work, although development and eventual commercialization will add costs.

Follow the Insider Money, but Respect the Risks

I like having specific developments to watch in all four companies.

Xenon has its epilepsy application at the FDA.

Relmada needs to finish its manufacturing work and get its pivotal program underway.

NeOnc has to turn promising early observations into stronger evidence.

MAIA has a randomized lung cancer trial that can test whether its approach delivers a meaningful benefit.

That list offers plenty of room for disappointment.

There is also room for a successful drug to change the value of a business dramatically.

Better trial results can increase the odds of approval and strengthen a company’s bargaining position well before it starts selling a medicine.

That is why these purchases interest me.

The executives know the remaining work is expensive and uncertain, yet they have put substantial personal money into the shares.

We still have to do our own homework and keep the positions sensible.

I want a successful drug to make a meaningful contribution to the portfolio.

I also intend to be around to buy the next opportunity if one of these fails.